74 Optical Coherence Tomography

Ophthalmol 130(5): 677-679.

**Chapter 4**

**Optical Coherence Tomography in Neuro-**

In optic nerve disease excluding glaucoma, mainly three ophthalmoscopic presentations of the optic disc can be encountered: an apparently normal optic disc, an atrophic or an edematous optic disc. Many documentation methods in optic neuropathy (ON) have been used: drawings;

The optical coherence tomography (OCT), based on interferometry analysis, is a major achievement particularly for documentation of quantitative changes in the optic nerve head: it allows a measure of the retinal nerve fiber layer thickness (RNFL). This retinal layer is composed of non myelinated axons (myelination is generally posterior to the cribriform lamina). OCT can quantify a decrease in thickness due to the atrophy by axonal loss or increase in thickness related to edema. This review aims to illustrate the usefulness of this RNFL

An extensive review of the literature on applications of OCT in optic neuropathy was per‐ formed. The PubMed search engine was applied to the keywords "optic neuropathy", "optical coherence tomography" and "retinal nerve fiber layer". Studies exploring the various diseases of the optic nerve were classified according to the OCT results obtained at the initial visit. Glaucomatous neuropathy was excluded from this review. Characteristic diseases are

> © 2013 Garcia et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

© 2013 Garcia et al.; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

distribution, and reproduction in any medium, provided the original work is properly cited.

quantification in the exploration of optic nerve and anterior visual pathway diseases.

Tony Garcia, Ghislain Bonnay, Ayman Tourbah and

Additional information is available at the end of the chapter

color, monochromatic and angiographic photographs.

**Ophthalmology**

http://dx.doi.org/10.5772/53510

**2. Materials and methods**

illustrated by clinical case reports.

Carl Arndt

**1. Introduction**

### **Optical Coherence Tomography in Neuro-Ophthalmology**

Tony Garcia, Ghislain Bonnay, Ayman Tourbah and Carl Arndt

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/53510

#### **1. Introduction**

In optic nerve disease excluding glaucoma, mainly three ophthalmoscopic presentations of the optic disc can be encountered: an apparently normal optic disc, an atrophic or an edematous optic disc. Many documentation methods in optic neuropathy (ON) have been used: drawings; color, monochromatic and angiographic photographs.

The optical coherence tomography (OCT), based on interferometry analysis, is a major achievement particularly for documentation of quantitative changes in the optic nerve head: it allows a measure of the retinal nerve fiber layer thickness (RNFL). This retinal layer is composed of non myelinated axons (myelination is generally posterior to the cribriform lamina). OCT can quantify a decrease in thickness due to the atrophy by axonal loss or increase in thickness related to edema. This review aims to illustrate the usefulness of this RNFL quantification in the exploration of optic nerve and anterior visual pathway diseases.

#### **2. Materials and methods**

An extensive review of the literature on applications of OCT in optic neuropathy was per‐ formed. The PubMed search engine was applied to the keywords "optic neuropathy", "optical coherence tomography" and "retinal nerve fiber layer". Studies exploring the various diseases of the optic nerve were classified according to the OCT results obtained at the initial visit. Glaucomatous neuropathy was excluded from this review. Characteristic diseases are illustrated by clinical case reports.

© 2013 Garcia et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 Garcia et al.; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **3. Results**

The average RNFL thickness is the most common parameter encountered in all publications. It represents the average of all measured thickness values in a predefined annular zone adjacent to the optic disc. In some publications, the macular volume has also been evaluated. Ophthalmoscopy noted normal appearance of the right optic disc and slight left optic disc hyperhemia (figure 1). Acute optic neuritis was suspected. On the OCT, there is a slight RNFL swelling in its nasal superior part, however the mean thickness remains within normal limits

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The left visual field was abnormal with a nasal inferior defect, the right visual field was normal

After stabilization of the affected eye following an episode of optic neuritis, average RNFL thickness is between 59.75 and 85.00 µm. In the contralateral eye, this parameter is between 82.73 and 99.80 µm (normal range: 102.90 - 111.10 µm) [5]. Thus, axonal loss is often present

in both eyes even if symptomatic optic neuritis affects one eye only.

(figure 2).

(figure 3).

**Figure 3.** Visual fields (case 1)

**Figure 2.** OCT slight RNFL swelling in the left eye (case 1)

The change over time of the average RNFL thickness could be characterized by two different patterns:

#### **4. Progressive decrease of RNFL thickness (evolution towards atrophy)**

#### **4.1. Inflammatory diseases: Multiple sclerosis (case reports 1 et 2)**

Multiple sclerosis (MS) is the most common cause of optic neuropathy, therefore the evaluation of RNFL thickness in MS was the subject of numerous publications [1,2]

At the initial stage of optic neuritis, RNFL thickness is within normal limits, after 2 months it decreases and stabilizes between 6 and 12 months [3,4] as highlighted in case report 1.

#### **Case report 1:**

A 35 year-old man was admitted for subacute left monocular impairment. Left orbital pain increased by ocular movements was reported. Visual acuity was 1.0 on the right eye and 0.4 in the left eye.

**Figure 1.** Retinal colour photography (case 1)

Ophthalmoscopy noted normal appearance of the right optic disc and slight left optic disc hyperhemia (figure 1). Acute optic neuritis was suspected. On the OCT, there is a slight RNFL swelling in its nasal superior part, however the mean thickness remains within normal limits (figure 2).

**Figure 2.** OCT slight RNFL swelling in the left eye (case 1)

The left visual field was abnormal with a nasal inferior defect, the right visual field was normal (figure 3).

**Figure 3.** Visual fields (case 1)

**3. Results**

78 Optical Coherence Tomography

patterns:

RNFL decrease

**Case report 1:**

in the left eye.

**Figure 1.** Retinal colour photography (case 1)

**•** an increased RNFL thickness at the initial visit.

The average RNFL thickness is the most common parameter encountered in all publications. It represents the average of all measured thickness values in a predefined annular zone adjacent to the optic disc. In some publications, the macular volume has also been evaluated. The change over time of the average RNFL thickness could be characterized by two different

**•** a normal RNFL thickness at the initial visit, followed by a gradual decrease: progressive

**4. Progressive decrease of RNFL thickness (evolution towards atrophy)**

Multiple sclerosis (MS) is the most common cause of optic neuropathy, therefore the evaluation

At the initial stage of optic neuritis, RNFL thickness is within normal limits, after 2 months it decreases and stabilizes between 6 and 12 months [3,4] as highlighted in case report 1.

A 35 year-old man was admitted for subacute left monocular impairment. Left orbital pain increased by ocular movements was reported. Visual acuity was 1.0 on the right eye and 0.4

**4.1. Inflammatory diseases: Multiple sclerosis (case reports 1 et 2)**

of RNFL thickness in MS was the subject of numerous publications [1,2]

After stabilization of the affected eye following an episode of optic neuritis, average RNFL thickness is between 59.75 and 85.00 µm. In the contralateral eye, this parameter is between 82.73 and 99.80 µm (normal range: 102.90 - 111.10 µm) [5]. Thus, axonal loss is often present in both eyes even if symptomatic optic neuritis affects one eye only.

#### **Case report 2**

A 54-year-old woman suffered from multiple sclerosis and had already a left demyelinating optic neuritis a few years ago. Flair-weighted axial magnetic resonance image shows periven‐ tricular plaques (figure 4).

On ophthalmoscopy, a left temporal disc pallor indicative of previous optic neuritis was noted

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**Figure 6.** Retinal colour photography: left optic disc pallor (case 2)

**Figure 7.** OCT: temporal RNFL thinning (case 2)

OCT could confirm the decrease of the left temporal RNFL (figure 7).

(figure 6).

**Figure 4.** Brain MRI scan (case 2)

Visual acuity was 1.0 in both eyes. Left visual field displayed a small inferior central defect.

**Figure 5.** Visual field (case 2)

On ophthalmoscopy, a left temporal disc pallor indicative of previous optic neuritis was noted (figure 6).

**Figure 6.** Retinal colour photography: left optic disc pallor (case 2)

**Case report 2**

80 Optical Coherence Tomography

tricular plaques (figure 4).

**Figure 4.** Brain MRI scan (case 2)

**Figure 5.** Visual field (case 2)

A 54-year-old woman suffered from multiple sclerosis and had already a left demyelinating optic neuritis a few years ago. Flair-weighted axial magnetic resonance image shows periven‐

Visual acuity was 1.0 in both eyes. Left visual field displayed a small inferior central defect.

OCT could confirm the decrease of the left temporal RNFL (figure 7).

**Figure 7.** OCT: temporal RNFL thinning (case 2)

However, the importance of RNFL loss depends on the severity of MS in which optic neuritis occurs.

the layer of ganglion fibers reflects an atrophy more severe and diffuse than that observed in MS, mainly in the upper and lower quadrants [19,20]. As in MS, there is a correlation between the retinal nerve fiber layer thickness and the overall neurological disability assessed by the EDSS [21]. OCT can thus provide morphological arguments in the differential diagnosis of Devic's syndrome and MS. In a comparative study, the average thickness was 63.60 µm in Devic's syndrome, whereas it is 88.30 µm in MS (102.00 µm in the group of MS patients in an eye with no history of optic neuropathy) [22]. The average RNFL loss is 15 µm in a patient

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A 35-year-old woman had bilateral optic neuritis. Left visual acuity was 1.0. Despite antiinflammatory treatment, right visual acuity had not recovered and remained very low (0.02).

Optic atrophy is observed in the right eye, there is an optic disc pallor in the left eye (figure 8)

suffering from MS, whereas it is 39.00 µm in the case of Devic's syndrome [22].

**Case 3**

**Figure 8.** Retinal colour photography (case 3)

In the eye affected by inaugural optic neuritis, the RNFL thickness stabilizes at 58.10 microns, and at 101.20 microns in the contralateral eye.

If optic neuritis occurs in patients presenting with a relapsing form of MS, RNFL loss is greater in the affected eye, stabilizing at an average thickness of 48.20 µm whereas the contralateral eye remains unaffected, the thickness remains at a high average level of 103.70 µm.

In secondary progressive forms, characterized by a continuous evolution toward a severe neurological disability, axonal loss is even greater in the affected eye of optic neuritis (39.50 µm on average), but also affects the contralateral eye (83.40 µm on average) [6]. This RNFL loss predominates in the temporal quadrant [3] [7], a clinical model demonstrating the coexistence of axonal loss and demyelinating lesions in MS.

Other parameters have been evaluated with OCT in MS, especially a decrease in macular volume which is correlated with axonal loss [8] [9]. The relationship between central and peripheral macular thickness is an indicator of the evolution of the disease [10]. In addition, in MS, RNFL loss is considered to be a fairly accurate indicator of overall axonal loss, both ocular and extraocular. In the early course of the disease, there is a correlation between the decrease in RNFL thickness and neurological disability assessed by the Expanded Disability Status Scale (EDSS) [11] which represents the global axonal loss in MS. There is a relationship between RNFL loss and brain atrophy [12]. Thus RNFL thickness also appears as a reliable marker of disease severity.

Finally, some correlations between OCT parameters and morphological and functional data have been reported.

At the initial stage of optic neuritis: when RNFL thickness is often normal, visual evoked potentials (VEP) (and MRI when it is rapidly accessible) is more efficient to objectify the optic nerve lesions (eliminating a pithiatism when there is a doubt). Thus, at the early stages of MS, OCT is less sensitive than VEP for detecting clinical and subclinical optic neuropathy [13].

At distance of the initial attack of optic neuritis

#### **4.2. Degenerative diseases: Neuromyelitis Optica (NMO) or Devic's disease (case report 3)**

In Devic's syndrome, unlike MS, optic neuropathy is severe and is associated with spinal cord lesions without brain damage (figure 10). In OCT, the significant decrease in the thickness of the layer of ganglion fibers reflects an atrophy more severe and diffuse than that observed in MS, mainly in the upper and lower quadrants [19,20]. As in MS, there is a correlation between the retinal nerve fiber layer thickness and the overall neurological disability assessed by the EDSS [21]. OCT can thus provide morphological arguments in the differential diagnosis of Devic's syndrome and MS. In a comparative study, the average thickness was 63.60 µm in Devic's syndrome, whereas it is 88.30 µm in MS (102.00 µm in the group of MS patients in an eye with no history of optic neuropathy) [22]. The average RNFL loss is 15 µm in a patient suffering from MS, whereas it is 39.00 µm in the case of Devic's syndrome [22].

#### **Case 3**

However, the importance of RNFL loss depends on the severity of MS in which optic neuritis

In the eye affected by inaugural optic neuritis, the RNFL thickness stabilizes at 58.10 microns,

If optic neuritis occurs in patients presenting with a relapsing form of MS, RNFL loss is greater in the affected eye, stabilizing at an average thickness of 48.20 µm whereas the contralateral

In secondary progressive forms, characterized by a continuous evolution toward a severe neurological disability, axonal loss is even greater in the affected eye of optic neuritis (39.50 µm on average), but also affects the contralateral eye (83.40 µm on average) [6]. This RNFL loss predominates in the temporal quadrant [3] [7], a clinical model demonstrating the

Other parameters have been evaluated with OCT in MS, especially a decrease in macular volume which is correlated with axonal loss [8] [9]. The relationship between central and peripheral macular thickness is an indicator of the evolution of the disease [10]. In addition, in MS, RNFL loss is considered to be a fairly accurate indicator of overall axonal loss, both ocular and extraocular. In the early course of the disease, there is a correlation between the decrease in RNFL thickness and neurological disability assessed by the Expanded Disability Status Scale (EDSS) [11] which represents the global axonal loss in MS. There is a relationship between RNFL loss and brain atrophy [12]. Thus RNFL thickness also appears as a reliable

Finally, some correlations between OCT parameters and morphological and functional data

At the initial stage of optic neuritis: when RNFL thickness is often normal, visual evoked potentials (VEP) (and MRI when it is rapidly accessible) is more efficient to objectify the optic nerve lesions (eliminating a pithiatism when there is a doubt). Thus, at the early stages of MS, OCT is less sensitive than VEP for detecting clinical and subclinical optic neuropathy [13].

**•** there is no correlation between RNFL thickness (a marker of axonal loss) and P100 latency (a marker of demyelination) [14]. In optic neuritis, the increase of cup/disc ratio is inversely proportional to the decrease in visual acuity and the decrease in RNFL thickness [15]; **•** there is a correlation between RNFL thickness (morphological marker of axonal loss) and visual acuity (a loss of one line of visual acuity corresponds to an average decrease of 5,40 µm in thickness) [16], pattern electroretinogram or pupillary reflex (functional markers of

**4.2. Degenerative diseases: Neuromyelitis Optica (NMO) or Devic's disease (case report 3)** In Devic's syndrome, unlike MS, optic neuropathy is severe and is associated with spinal cord lesions without brain damage (figure 10). In OCT, the significant decrease in the thickness of

eye remains unaffected, the thickness remains at a high average level of 103.70 µm.

occurs.

82 Optical Coherence Tomography

and at 101.20 microns in the contralateral eye.

marker of disease severity.

axonal loss) [17, 18].

At distance of the initial attack of optic neuritis

have been reported.

coexistence of axonal loss and demyelinating lesions in MS.

A 35-year-old woman had bilateral optic neuritis. Left visual acuity was 1.0. Despite antiinflammatory treatment, right visual acuity had not recovered and remained very low (0.02).

**Figure 8.** Retinal colour photography (case 3)

Optic atrophy is observed in the right eye, there is an optic disc pallor in the left eye (figure 8)

Transverse myelitis was found on the MRI scan (Figure 10) as part of Devic's disease.

Compression of visual pathways caused by a pituitary adenoma induces axonal loss respon‐ sible for RNFL loss on time domain OCT. The importance of this axonal loss predicts visual acuity changes and visual field recovery after surgery for pituitary adenoma [23]. The postoperative recovery is significantly better if the preoperative thickness is greater than 85.00

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A 75 year-old man complained of chronic headache. Visual acuity was 0.8 on the right eye and

**4.3. Compressive disease (case 4)**

**Figure 11.** Visual field: temporal asymmetric defect in both eyes (case 4)

Visual fields showed temporal defects in particular in the left field (Figure 11).

µm [24].

**Case 4**

0.4 in the left one.

**Figure 12.** Brain MRI scan (case 4)

**Figure 9.** OCT RNFL: loss in the right eye (case 3)

Important decrease of retinal fiber layer was found on the right OCT with an average thickness of 65 µm (figure 9).

**Figure 10.** Brain and Medullar MRI scan (case 3)

Transverse myelitis was found on the MRI scan (Figure 10) as part of Devic's disease.

#### **4.3. Compressive disease (case 4)**

Compression of visual pathways caused by a pituitary adenoma induces axonal loss respon‐ sible for RNFL loss on time domain OCT. The importance of this axonal loss predicts visual acuity changes and visual field recovery after surgery for pituitary adenoma [23]. The postoperative recovery is significantly better if the preoperative thickness is greater than 85.00 µm [24].

#### **Case 4**

**Figure 9.** OCT RNFL: loss in the right eye (case 3)

**Figure 10.** Brain and Medullar MRI scan (case 3)

of 65 µm (figure 9).

84 Optical Coherence Tomography

Important decrease of retinal fiber layer was found on the right OCT with an average thickness

A 75 year-old man complained of chronic headache. Visual acuity was 0.8 on the right eye and 0.4 in the left one.

**Figure 11.** Visual field: temporal asymmetric defect in both eyes (case 4)

Visual fields showed temporal defects in particular in the left field (Figure 11).

**Figure 12.** Brain MRI scan (case 4)

Magnetic resonance imaging discovered a large pituitary tumor with chiasm compression (figure 12).

Preoperative average RNFL thickness attests of significant axonal loss in the temporal area.

**Figure 14.** Retinal colour photography (case 5): bilateral optic atrophy

**Figure 15.** Farnsworth 15HUE (case 5): yellow blue defect

On color vision testing there is a blue-yellow confusion axis (Figure 15).

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On the time domain OCT, a major bilateral RNFL loss is noted (Figure 16).

**Figure 13.** OCT: temporal RNFL thinning (case 4)

#### **4.4. Hereditary disease**

#### *4.4.1. Dominant Optic Atrophy (DOA) or Kjer's disease (Case 5)*

In dominant optic atrophy (DOA), there is bilateral symmetric optic nerve pallor (Case 5) related to retinal ganglion cell death. The decrease in the RNFL thickness in OCT is dominant in the temporal part [25].

#### **Case 5**

A seven year old girl is referred for poor visual acuity (RE 20/40, LE 20/50) associated with bilateral optic disc atrophy (Figure 14).

**Figure 14.** Retinal colour photography (case 5): bilateral optic atrophy

Magnetic resonance imaging discovered a large pituitary tumor with chiasm compression

Preoperative average RNFL thickness attests of significant axonal loss in the temporal area.

(figure 12).

86 Optical Coherence Tomography

**Figure 13.** OCT: temporal RNFL thinning (case 4)

bilateral optic disc atrophy (Figure 14).

*4.4.1. Dominant Optic Atrophy (DOA) or Kjer's disease (Case 5)*

In dominant optic atrophy (DOA), there is bilateral symmetric optic nerve pallor (Case 5) related to retinal ganglion cell death. The decrease in the RNFL thickness in OCT is dominant

A seven year old girl is referred for poor visual acuity (RE 20/40, LE 20/50) associated with

**4.4. Hereditary disease**

in the temporal part [25].

**Case 5**

On color vision testing there is a blue-yellow confusion axis (Figure 15).

**Figure 15.** Farnsworth 15HUE (case 5): yellow blue defect

On the time domain OCT, a major bilateral RNFL loss is noted (Figure 16).

A dominant pattern was found upon family enquiry (Figure 18).

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**Figure 18.** Family enquiry (case 5)

**4.5. Toxic optic neuropathy**

OCT.

**Case 6**

*4.4.2. Other hereditary optic neuropathies*

In the authors' clinical experience, OCT is also useful in the morphological evaluation of optic neuropathies encountered in other hereditary diseases such as recessive optic neuropathy and

OCT can be useful for the follow-up of visual loss in patients with toxic optic neuropathy due to smoking, alcohol consumption or treatment for tuberculosis. In the early stages of toxic optic neuropathy, RNFL edema may be detected in some patients before permanent visual loss occurs. RNFL decrease consecutive to the withdrawal of the toxic agent can be monitored with

A 48-year-old woman complained of progressive and painless visual loss. She had alcohol and tobacco addiction. She was deficient in B vitamins. Visual acuity was 0.3 in the right eye and 0.4 in the left eye. Color fundus photos showed pale optic discs without hemorrhage. Miliary

Wolfram's disease. However no reports on this subject could be found.

drusens were also observed on macular areas (Figure 19).

**Figure 16.** OCT: RNFL loss in both eyes (case 5)

There is no compressive process on the brain MRI which only displays atrophic optic nerves (figure 17).

**Figure 17.** Brain MRI scan (case 5): bilateral thinning of the optic nerves

A dominant pattern was found upon family enquiry (Figure 18).

**Figure 18.** Family enquiry (case 5)

#### *4.4.2. Other hereditary optic neuropathies*

In the authors' clinical experience, OCT is also useful in the morphological evaluation of optic neuropathies encountered in other hereditary diseases such as recessive optic neuropathy and Wolfram's disease. However no reports on this subject could be found.

#### **4.5. Toxic optic neuropathy**

OCT can be useful for the follow-up of visual loss in patients with toxic optic neuropathy due to smoking, alcohol consumption or treatment for tuberculosis. In the early stages of toxic optic neuropathy, RNFL edema may be detected in some patients before permanent visual loss occurs. RNFL decrease consecutive to the withdrawal of the toxic agent can be monitored with OCT.

#### **Case 6**

**Figure 16.** OCT: RNFL loss in both eyes (case 5)

**Figure 17.** Brain MRI scan (case 5): bilateral thinning of the optic nerves

(figure 17).

88 Optical Coherence Tomography

There is no compressive process on the brain MRI which only displays atrophic optic nerves

A 48-year-old woman complained of progressive and painless visual loss. She had alcohol and tobacco addiction. She was deficient in B vitamins. Visual acuity was 0.3 in the right eye and 0.4 in the left eye. Color fundus photos showed pale optic discs without hemorrhage. Miliary drusens were also observed on macular areas (Figure 19).

**Figure 19.** Retinal colour photography (case 6): bilateral optic atrophy

Centrocaecal scotomas were visible in both visual fields (Figure 20)

**Figure 21.** OCT RNFL: loss in both eyes (case 6)

**5.1. Papilledema (case 7)**

**Case 7**

**5. Gradual RNFL reduction following initial increase of RNFL thickness**

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Depending on the underlying disease, the condition will either resolve with normalization or

Optic disc swelling due to idiopathic intracranial hypertension is referred to as papilledema [26]. It may be responsible for the deterioration of visual function and progression to optic atrophy. Visual field and VEP are prognostic indicators for visual outcome [27]. This is not the case for RNFL thickness changes which only enable to monitor the progression of the disease.

A 28-year-old woman suffered from headache and vomiting. On ophthalmologic examination, visual acuity was 0.9 on the right eye and 1.0 on the left eye without oculomotor paralysis. This

In optic disc swelling, an increase in the RNFL thickness can be quantified by OCT.

shift to optic atrophy with axonal loss. This evolution can be monitored with OCT.

**Figure 20.** Visual fields (case 6)

OCT confirmed optic nerve atrophy demonstrating a global RNFL loss.

**Figure 21.** OCT RNFL: loss in both eyes (case 6)

#### **5. Gradual RNFL reduction following initial increase of RNFL thickness**

In optic disc swelling, an increase in the RNFL thickness can be quantified by OCT.

Depending on the underlying disease, the condition will either resolve with normalization or shift to optic atrophy with axonal loss. This evolution can be monitored with OCT.

#### **5.1. Papilledema (case 7)**

Optic disc swelling due to idiopathic intracranial hypertension is referred to as papilledema [26]. It may be responsible for the deterioration of visual function and progression to optic atrophy. Visual field and VEP are prognostic indicators for visual outcome [27]. This is not the case for RNFL thickness changes which only enable to monitor the progression of the disease.

#### **Case 7**

**Figure 19.** Retinal colour photography (case 6): bilateral optic atrophy

**Figure 20.** Visual fields (case 6)

90 Optical Coherence Tomography

Centrocaecal scotomas were visible in both visual fields (Figure 20)

OCT confirmed optic nerve atrophy demonstrating a global RNFL loss.

A 28-year-old woman suffered from headache and vomiting. On ophthalmologic examination, visual acuity was 0.9 on the right eye and 1.0 on the left eye without oculomotor paralysis. This condition was due to intracranial hypertension. A bilateral papilloedema, venous engorge‐ ment, white exudates and superficial retinal folds was found (Figure 22).

**5.2. Anterior Ischemic Optic Neuropathy (AION)**

atrophy occurs without excavation [29,30].

**Figure 25.** Retinal colour photography (case 8)

slowly decreased as optic atrophy developed.

**Case 8**

decreased.

At the initial stage of an anterior ischemic optic neuropathy, there is most often a progressive optic disc swelling. Then, axonal loss is responsible for a gradual reduction of RNFL leading

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At the acute phase, Leber's hereditary optic neuropathy associates peripapillary telangiectasia, tortuosity of retinal vessels and a peripapillary RNFL swelling with apparent optic disc swelling (figure 25-27). Within a few months (generally less than six months), diffuse optic

An 11-year-old girl with no family history of Leber's disease suddenly presented with severe painless central vision loss in the right eye. Dilated capillaries in the retina adjacent to the optic nerve head were found in both eyes. Two months after onset, visual acuity in the left eye also

Average RNFL thickness was increased in both eyes on the initial examination and it then

to a variable stage of optic atrophy stabilizing at six months of onset [28].

**5.3. Leber's Hereditary Optic Neuropathy (LHON) (case 8)**

**Figure 22.**

**Figure 23.** Visual fields (case 7)

After spinal puncture and acetazolamide medication, she recovered normal visual acuity. OCT follow-up enabled to monitor the improvement with treatment (Figure 24).

**Figure 24.** OCT RNFL follow-up (case 7)

#### **5.2. Anterior Ischemic Optic Neuropathy (AION)**

At the initial stage of an anterior ischemic optic neuropathy, there is most often a progressive optic disc swelling. Then, axonal loss is responsible for a gradual reduction of RNFL leading to a variable stage of optic atrophy stabilizing at six months of onset [28].

#### **5.3. Leber's Hereditary Optic Neuropathy (LHON) (case 8)**

At the acute phase, Leber's hereditary optic neuropathy associates peripapillary telangiectasia, tortuosity of retinal vessels and a peripapillary RNFL swelling with apparent optic disc swelling (figure 25-27). Within a few months (generally less than six months), diffuse optic atrophy occurs without excavation [29,30].

#### **Case 8**

condition was due to intracranial hypertension. A bilateral papilloedema, venous engorge‐

After spinal puncture and acetazolamide medication, she recovered normal visual acuity. OCT

follow-up enabled to monitor the improvement with treatment (Figure 24).

ment, white exudates and superficial retinal folds was found (Figure 22).

**Figure 22.**

**Figure 23.** Visual fields (case 7)

92 Optical Coherence Tomography

**Figure 24.** OCT RNFL follow-up (case 7)

An 11-year-old girl with no family history of Leber's disease suddenly presented with severe painless central vision loss in the right eye. Dilated capillaries in the retina adjacent to the optic nerve head were found in both eyes. Two months after onset, visual acuity in the left eye also decreased.

**Figure 25.** Retinal colour photography (case 8)

Average RNFL thickness was increased in both eyes on the initial examination and it then slowly decreased as optic atrophy developed.

**5.4. Secondary intracranial hypertension**

**Case 9**

(figure 28).

monitor RNFL thickness reduction after causal treatment.

**Figure 28.** Retinal colour photography (case 9): Optic nerve head swelling

superior optic atrophy (figure 30).

**6. Limitations**

Goldmann visual fields displayed inferior altitudinal field defects (Figure 29).

several limitation inherent to the device which should be highlighted.

Serological tests on blood and cerebrospinal fluid confirmed a syphilitic infection. After initial intravenous penicillin G, the patient was discharged with ceftriaxone injections (1 g/day) for three weeks. On the OCT scans, the decrease of optic nerve head swelling was replaced with

Although OCT provides very useful quantitative information on RNFL thickness, there are

Many different diseases can be responsible for increased intracranial pressure such as infec‐ tious meningitis (case 9). As in other diseases with initial optic disc swelling, OCT enables to

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A 47-year-old man was admitted for visual field disorders with papulosquamous eruption of the palms and soles within two weeks following a previous asymptomatic general skin eruption. Visual acuity was 0.8 in both eyes. Bilateral optic nerve head swelling was observed

**Figure 26.** Initial OCT RNFL (case 8)

**Figure 27.** End stage OCT RNFL (case 8)

#### **5.4. Secondary intracranial hypertension**

Many different diseases can be responsible for increased intracranial pressure such as infec‐ tious meningitis (case 9). As in other diseases with initial optic disc swelling, OCT enables to monitor RNFL thickness reduction after causal treatment.

#### **Case 9**

**Figure 26.** Initial OCT RNFL (case 8)

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**Figure 27.** End stage OCT RNFL (case 8)

A 47-year-old man was admitted for visual field disorders with papulosquamous eruption of the palms and soles within two weeks following a previous asymptomatic general skin eruption. Visual acuity was 0.8 in both eyes. Bilateral optic nerve head swelling was observed (figure 28).

**Figure 28.** Retinal colour photography (case 9): Optic nerve head swelling

Goldmann visual fields displayed inferior altitudinal field defects (Figure 29).

Serological tests on blood and cerebrospinal fluid confirmed a syphilitic infection. After initial intravenous penicillin G, the patient was discharged with ceftriaxone injections (1 g/day) for three weeks. On the OCT scans, the decrease of optic nerve head swelling was replaced with superior optic atrophy (figure 30).

#### **6. Limitations**

Although OCT provides very useful quantitative information on RNFL thickness, there are several limitation inherent to the device which should be highlighted.

**7. Discussion**

evoked potentials).

**Author details**

Tony Garcia1

**References**

20, 167-173.

**8. Declaration of interest**

, Ghislain Bonnay2

As in macular disease, OCT has become a precious tool that contributes to improve manage‐ ment of optic nerve disease. This review illustrates the many indications in neuro-ophthal‐ mology, although there are limitations to its use. OCT measures RNFL thickness to assess axonal loss [31]. Axonal loss may be masked in cases with optic nerve head swelling due to

Optical Coherence Tomography in Neuro-Ophthalmology

http://dx.doi.org/10.5772/53510

97

Despite the high utility of OCT in neuro-ophthalmology, exclusive RNFL thickness analysis is not sufficient for assessing optic nerve disease. OCT results should always be interpreted in the light of clinical ophthalmoloscopy and visual function (visual acuity, perimetry, visual

the inhibition of orthograde axoplasmic transport at the initial stage of the disease.

The authors hereby declare that they have no conflict of interest related to this article.

, Ayman Tourbah3

1 Ophtalmologie, Hôpital Robert Debré, Reims University Hospital, Reims, France

3 Service de Neurologie, Hôpital Maison Blanche, Reims University Hospital, Reims, France

[1] Garcia-martin, E, Pueyo, V, Martin, J, & Fernandez, F. J. Progressive changes in the retinal nerve fiber layer in patients with multiple sclerosis. Eur J Ophthalmol (2010). ,

[2] Beddiaf, A, & De Sèze, J. Névrite optique dans la sclérose en plaques : données diag‐

[3] Costello, F, Hodge, W, Pan, Y. I, Eggenberger, E, Coupland, S, & Kardon, R. H. Tracking retinal nerve fiber layer loss after optic neuritis: a prospective study using

2 Service d'Ophtalmologie, Troyes General Hospital, Troyes, France

nostiques et pronostiques. Rev Neurol (2009). SS147, 145.

optical coherence tomography. Mult Scler (2008). , 14, 893-905.

and Carl Arndt1

**Figure 29.** Visual fields (case 9)

**Figure 30.** OCT RNFL follow-up (case 9)

#### **6.1. Age**

In the OCT database, normal values apply only to patients over 18 years. Evaluation of RNFL thickness is based on the assumption that there are no significant changes in normals from birth to the age of 18.

#### **6.2. Morphological variations**

RNFL thickness evaluation by OCT is not a reliable method in case of major morphologic changes of the optic nerve head such peripapillary atrophy in high myopia, staphyloma or optic pits.

#### **6.3. Refractive media disorders**

Ultra-red light has to pass through the transparent media of the eye to reach the retina. In case of corneal dystrophy, cataract, vitreous opacity, there is a signal decrease and RNFL thickness measurements become less reliable.

#### **7. Discussion**

As in macular disease, OCT has become a precious tool that contributes to improve manage‐ ment of optic nerve disease. This review illustrates the many indications in neuro-ophthal‐ mology, although there are limitations to its use. OCT measures RNFL thickness to assess axonal loss [31]. Axonal loss may be masked in cases with optic nerve head swelling due to the inhibition of orthograde axoplasmic transport at the initial stage of the disease.

Despite the high utility of OCT in neuro-ophthalmology, exclusive RNFL thickness analysis is not sufficient for assessing optic nerve disease. OCT results should always be interpreted in the light of clinical ophthalmoloscopy and visual function (visual acuity, perimetry, visual evoked potentials).

#### **8. Declaration of interest**

The authors hereby declare that they have no conflict of interest related to this article.

#### **Author details**

Tony Garcia1 , Ghislain Bonnay2 , Ayman Tourbah3 and Carl Arndt1

#### **References**

**6.1. Age**

optic pits.

birth to the age of 18.

**Figure 29.** Visual fields (case 9)

96 Optical Coherence Tomography

**6.2. Morphological variations**

**Figure 30.** OCT RNFL follow-up (case 9)

**6.3. Refractive media disorders**

measurements become less reliable.

In the OCT database, normal values apply only to patients over 18 years. Evaluation of RNFL thickness is based on the assumption that there are no significant changes in normals from

RNFL thickness evaluation by OCT is not a reliable method in case of major morphologic changes of the optic nerve head such peripapillary atrophy in high myopia, staphyloma or

Ultra-red light has to pass through the transparent media of the eye to reach the retina. In case of corneal dystrophy, cataract, vitreous opacity, there is a signal decrease and RNFL thickness

[4] Costello, F, Coupland, S, Hodge, W, Lorello, G. R, Koroluk, J, Pan, Y. I, et al. Quanti‐ fying axonal loss after optic neuritis with optical coherence tomography. Ann Neurol (2006). , 59, 963-969.

[16] Noval, S, Contreras, I, Rebolleda, G, & Muñoz-negrete, F. J. Optical coherence tomog‐ raphy versus automated perimetry for follow-up of optic neuritis. Acta Ophthalmol

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[17] Parisi, V, Manni, G, Spadaro, M, Colacino, G, Restuccia, R, Marchi, S, et al. Correla‐ tion between morphological and functional retinal impairment in multiple sclerosis

[18] Salter, A. R, Conger, A, Frohman, T. C, Zivadinov, R, Eggenberger, E, Calabresi, P, et al. Retinal architecture predicts pupillary reflex metrics in MS. Mult Scler (2009). , 15,

[19] Green, A. J, & Cree, B. A. Distinctive retinal nerve fibre layer and vascular changes in neuromyelitis optica following optic neuritis. J Neurol Neurosurg Psychiatry (2009). ,

[20] Naismith, R. T, Tutlam, N. T, Xu, J, Klawiter, E. C, Shepherd, J, Trinkaus, K, et al. Op‐ tical coherence tomography differs in neuromyelitis optica compared with multiple

[21] De Seze, J, Blanc, F, Jeanjean, L, Zéphir, H, Labauge, P, Bouyon, M, et al. Optical co‐ herence tomography in neuromyelitis optica. Arch Neurol (2008). , 65, 920-923. [22] Ratchford, J. N, Quigg, M. E, Conger, A, Frohman, T, Frohman, E, Balcer, L. J, et al. Optical coherence tomography helps differentiate neuromyelitis optica and MS optic

[23] Savino, P. J. Evaluation of the retinal nerve fiber layer: descriptive or predictive? J

[24] Danesh-meyer, H. V, Papchenko, T, Savino, P. J, Law, A, Evans, J, & Gamble, G. D. In vivo retinal nerve fiber layer thickness measured by optical coherence tomography predicts visual recovery after surgery for parachiasmal tumors. Invest Ophthalmol

[25] Hamel, C, & Lenaers, G. Neuropathies optiques héréditaires. EMC (Elsevier Masson

[26] Walsh and Hoyt's Clinical Neuro-Ophtalmology PhiladelphiaPA, USA: Lippincott

[27] Biousse, V, & Newman, N. J. Management of optic nerve disorders: part II. Idiopath‐

[28] Contreras, I, Noval, S, Rebolleda, G, & Muñoz-negrete, F. J. Follow-up of nonarteritic anterior ischemic optic neuropathy with optical coherence tomography. Ophthalmol‐

[29] Votruba, M. Inherited optic neuropathies. Pediatric Ophtalmology, Neuro-Ophtal‐

patients. Invest Ophthalmol Vis Sci (1999). , 40, 2520-2527.

sclerosis. Neurology (2009). , 72, 1077-1082.

neuropathies. Neurology (2009). , 73, 302-308.

SAS, Paris), Ophtalmologie, 21-480-E-30, (2007).

ic intracranial hypertension. Drugs Today (1997). , 33, 19-24.

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Neuroophthalmol (2009). , 29, 245-249.

Williams & Wilkins ((1998). , 487-548.

Vis Sci (2008). , 49, 1879-1885.

ogy (2007). , 114, 2338-2344.

Scand (2006). , 84, 790-794.

479-486.

80, 1002-1005.

[16] Noval, S, Contreras, I, Rebolleda, G, & Muñoz-negrete, F. J. Optical coherence tomog‐ raphy versus automated perimetry for follow-up of optic neuritis. Acta Ophthalmol Scand (2006). , 84, 790-794.

[4] Costello, F, Coupland, S, Hodge, W, Lorello, G. R, Koroluk, J, Pan, Y. I, et al. Quanti‐ fying axonal loss after optic neuritis with optical coherence tomography. Ann Neurol

[5] Kallenbach, K, & Frederiksen, J. Optical coherence tomography in optic neuritis and

[6] Costello, F, Hodge, W, Pan, Y. I, Freedman, M, & Demeulemeester, C. Differences in retinal nerve fiber layer atrophy between multiple sclerosis subtypes. J Neurol Sci

[7] Pro, M. J, Pons, M. E, Liebmann, J. M, Ritch, R, Zafar, S, Lefton, D, et al. Imaging of the optic disc and retinal nerve fiber layer in acute optic neuritis. J Neurol Sci (2006). ,

[8] Burkholder, B. M, Osborne, B, Loguidice, M. J, Bisker, E, Frohman, T. C, Conger, A, et al. Macular volume determined by optical coherence tomography as a measure of

[9] Pulicken, M, Gordon-lipkin, E, Balcer, L. J, Frohman, E, Cutter, G, & Calabresi, P. A. Optical coherence tomography and disease subtype in multiple sclerosis. Neurology

[10] Gugleta, K, Mehling, M, Kochkorov, A, Grieshaber, M, Katamay, R, Flammer, J, et al. Pattern of macular thickness changes measured by ocular coherence tomography in patients with multiple sclerosis. Klin Monatsbl Augenheilkd (2008). , 225, 408-412. [11] Outteryck, O, Zephir, H, Defoort, S, Bouyon, M, Debruyne, P, Bouacha, I, et al. Opti‐ cal coherence tomography in clinically isolated syndrome: no evidence of subclinical

[12] Siger, M, Dziegielewski, K, Jasek, L, Bieniek, M, Nicpan, A, Nawrocki, J, et al. Optical coherence tomography in multiple sclerosis: thickness of the retinal nerve fiber layer as a potential measure of axonal loss and brain atrophy. J Neurol (2008). , 255,

[13] Naismith, R. T, Tutlam, N. T, Xu, J, Shepherd, J. B, Klawiter, E. C, Song, S. K, et al. Optical coherence tomography is less sensitive than visual evoked potentials in optic

[14] Gundogan, F. C, Demirkaya, S, & Sobaci, G. Is optical coherence tomography really a new biomarker candidate in multiple sclerosis? A structural and functional evalua‐

[15] Rebolleda, G, Noval, S, Contreras, I, Arnalich-montiel, F, García-perez, J. L, & Mu‐ ñoz-negrete, F. J. Optic disc cupping after optic neuritis evaluated with optic coher‐

neuronal loss in multiple sclerosis. Arch Neurol (2009). , 66, 1366-1372.

retinal axonal loss. Arch Neurol (2009). , 66, 1373-1377.

tion. Invest Ophthalmol Vis Sci (2007). , 48, 5773-5781.

neuritis. Neurology (2009). , 73, 46-52.

ence tomography. Eye (2009). , 23, 890-894.

multiple sclerosis: a review. Eur J Neurol (2007). , 14, 841-849.

(2006). , 59, 963-969.

98 Optical Coherence Tomography

(2009). , 281, 74-79.

(2007). , 69, 2085-2092.

250, 114-119.

1555-1560.

[30] Subei, A. M, & Eggenberger, E. R. Optical coherence tomography: another useful tool in a neuro-ophthalmologist's armamentarium. Curr Opin Ophthalmol (2009). , 20, 462-466.

**Section 2**

**Atherosclerosis**

[31] Pula, J. H, & Reder, A. T. Multiple sclerosis. Part I: neuro-ophthalmic manifestations. Curr Opin Ophthalmol (2009). , 20, 467-475.

**Section 2**

### **Atherosclerosis**

[30] Subei, A. M, & Eggenberger, E. R. Optical coherence tomography: another useful tool in a neuro-ophthalmologist's armamentarium. Curr Opin Ophthalmol (2009). , 20,

[31] Pula, J. H, & Reder, A. T. Multiple sclerosis. Part I: neuro-ophthalmic manifestations.

Curr Opin Ophthalmol (2009). , 20, 467-475.

462-466.

100 Optical Coherence Tomography

**Chapter 5**

**Visualization of Plaque Neovascularization by OCT**

Although the introduction of drug-eluting-stents (DES) has dramatically reduced restenosis and the need for repeat revascularization compared with bare-metal stents (BMS), percutane‐ ous coronary intervention (PCI) does not always prevent cardiac events, including acute coro‐ nary syndrome (ACS) [1]. Therefore, for all cardiologists, the detection of vulnerable plaques before they rupture is one of ultimate goals to predict and prevent ACS. Vulnerable plaques are characterized as thin fibrous cap (<65 µm), large lipid core, and macrophage infiltration within the cap. Furthermore, plaque neovascularization has been identified recently as a common fea‐ ture of plaque vulnerability. Increased neovascularization in atherosclerotic plaques plays an important role in plaque progression, plaque instability, and rupture of plaque [2-5]. Until re‐ cently, however, in vivo studies assessing neovascularization in atherosclerotic plaques have been difficult because of the lack of sufficient resolution that reliably identifies this feature of vulnerable plaque. The first-generation catheter-based Time-domain optical coherence tomog‐ raphy (TD-OCT) system (M2 and M3 OCT system; LightLab Imaging, Westford, MA, USA), which offers superior resolution of 10-15 µm, has emerged as an intracoronary imaging modal‐ ity, rendering the detailed micro-structure information of coronary plaques [6-8]. With its ex‐ cellent resolution, OCT may provide an opportunity to directly detect plaque neovascularization in vivo. This chapter reviews the evidence of plaque neovascularization ac‐

cumulated so far on OCT and discuss the future perspectives and limitations.

Nourishment of normal blood vessels is accomplished by oxygen diffusion from the vessel lumen or from adventitial vasa vasorum [9]. As atherosclerosis progresses, the intima thick‐ ens, and oxygen diffusion is impaired. As a result, vasa vasorum proliferates in the inner

> © 2013 Kitabata and Akasaka; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2013 Kitabata and Akasaka; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

**2. Neovascularization in atherosclerosis**

Hironori Kitabata and Takashi Akasaka

http://dx.doi.org/10.5772/53051

**1. Introduction**

Additional information is available at the end of the chapter

### **Visualization of Plaque Neovascularization by OCT**

Hironori Kitabata and Takashi Akasaka

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/53051

#### **1. Introduction**

Although the introduction of drug-eluting-stents (DES) has dramatically reduced restenosis and the need for repeat revascularization compared with bare-metal stents (BMS), percutane‐ ous coronary intervention (PCI) does not always prevent cardiac events, including acute coro‐ nary syndrome (ACS) [1]. Therefore, for all cardiologists, the detection of vulnerable plaques before they rupture is one of ultimate goals to predict and prevent ACS. Vulnerable plaques are characterized as thin fibrous cap (<65 µm), large lipid core, and macrophage infiltration within the cap. Furthermore, plaque neovascularization has been identified recently as a common fea‐ ture of plaque vulnerability. Increased neovascularization in atherosclerotic plaques plays an important role in plaque progression, plaque instability, and rupture of plaque [2-5]. Until re‐ cently, however, in vivo studies assessing neovascularization in atherosclerotic plaques have been difficult because of the lack of sufficient resolution that reliably identifies this feature of vulnerable plaque. The first-generation catheter-based Time-domain optical coherence tomog‐ raphy (TD-OCT) system (M2 and M3 OCT system; LightLab Imaging, Westford, MA, USA), which offers superior resolution of 10-15 µm, has emerged as an intracoronary imaging modal‐ ity, rendering the detailed micro-structure information of coronary plaques [6-8]. With its ex‐ cellent resolution, OCT may provide an opportunity to directly detect plaque neovascularization in vivo. This chapter reviews the evidence of plaque neovascularization ac‐ cumulated so far on OCT and discuss the future perspectives and limitations.

#### **2. Neovascularization in atherosclerosis**

Nourishment of normal blood vessels is accomplished by oxygen diffusion from the vessel lumen or from adventitial vasa vasorum [9]. As atherosclerosis progresses, the intima thick‐ ens, and oxygen diffusion is impaired. As a result, vasa vasorum proliferates in the inner

© 2013 Kitabata and Akasaka; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 Kitabata and Akasaka; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

layers of the vessel wall, and becomes major source of nutrients. Vasa vasorum neovascula‐ rization in early atherosclerosis is associated with inflammatory cell infiltration and lipid deposition, leading to plaque progression [10]. Furthermore, intraplaque hemorrhage from microvessels contributes to expansion of the necrotic core through the accumulation of free cholesterol from erythrocyte membranes. Several human pathologic studies have demon‐ strated that plaque neovascularization is pronounced among patients with unstable coro‐ nary syndromes and that its presence may be a marker of plaque instability and plaque rupture [4, 5, 11]. Therefore, investigations of imaging methods with the ability to visualize neovascularization would appear worthwhile.

characteristics of vulnerability such as positive remodeling and thin fibrous caps compared with plaques without these structures. Of note, the presence of increased microchannel counts was correlated with a greater frequency of thin-capped fibroatheroma (TCFA) (Figure 2). More recently, in larger study population (356 plaques in 117 patients), Tian et al investigated the clinical significance of intra-plaque neovascularization in culprit lesions and no-culprit le‐ sions of unstable angina pectoris (UAP) and in lesions of stable angina pectoris (SAP) using OCT [22]. Intra-plaque neovascularization was found in 35% of UAP culprit lesions, in 34% of UAP non-culprit lesions, and in 28% of SAP lesions, with no significant difference. Among UAP culprit lesions, plaques with neovessel had thinner fibrous cap thickness (56±20 µm vs. 75±30 µm, p<0.001) and significantly higher incidence of TCFA (81% vs. 47%, p=0.002) com‐ pared with those without neovessel. In addition, plaque burden was significantly bigger in UAP culprit lesions with neovascularization (79.8±7.9% vs. 72.8±10.7%, p=0.024). In terms of the non-culprit lesions of UAP patients and lesions of SAP patients, however, no significant difference in plaque characteristics was observed, regardless of the presence or absence of neo‐ vascularization. Interestingly, Kato et al reported that although the overall prevalence of mi‐ crochannel in non-culprit lesions was not significantly different between ACS and non-ACS patients (64.7% versus 55.2%, respectively, P=0.647), the closest distance from the lumen to mi‐ crochannel was shorter in ACS subjects than in non-ACS (104.6±67.0 µm versus 198.3±133.0 µm, p=0.027) [23]. The authors speculated that because neovascular networks expand from the adventitia into the intima as disease progresses [26], plaques with neovascularization located closer to the lumen might represent an advanced stage of atherosclerosis. Furthermore, Ue‐ mura et al revealed that microchannel structure in non-culprit plaques (defined as percent di‐ ameter stenosis of < 50%) identified by OCT is a predictor of subsequent plaque progression in

Visualization of Plaque Neovascularization by OCT

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105

**Figure 1.** OCT (M2 system) images of plaque neovessels. Microvessels in the outer plaque (A) near the adventitia and

(B) within the thickened intima can appear as signal-poor voids (white arrows) that are sharply delineated.

patients with coronary artery disease [24].

#### **3. Potential imaging modalities of neovascularization**

Several imaging modalities such as micro-computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound have emerged as potential techniques for imaging neoves‐ sels in atherosclerotic plaques. Micro-CT provides high-resolution images of coronary vasa vasorum neovascularization and insight into their structure and function in animal models [12, 13]. Winter et al have reported that molecular MRI with αvβ3-targeted, paramagnetic nanoparticles can detect plaque neovessels in atherosclerotic rabbit model [14]. In addition, more recently, Sirol et al have demonstrated how gadofluorine M-enhanced MRI can accu‐ rately identify plaque neovascularization in an animal model of atherosclerosis with good histological correlation [15]. Thus, even though the results from these techniques are prom‐ ising, further studies are needed for clinical application in humans. Intravascular ultrasound (IVUS) has the potential to detect flow within the plaque and subsequently evaluate func‐ tional neovessels. The development of IVUS-based imaging has recently demonstrated the preliminary data imaging neovascularization in coronary plaques in vivo after intravascular injection of microbubbles [16,17], but further investigations will be required to show the fea‐ sibility of this method for routine clinical use.

#### **4. Plaque neovascularization by OCT**

OCT has been proposed as a high-resolution imaging modality that can identify micro-struc‐ tures in atherosclerotic plaques [8, 18, 19]. The superb high-resolution of OCT may offer an op‐ portunity of studying the spatial distribution of plaque neovascularization in vivo (Figure 1) [20]. In fact, it has been shown that OCT is able to visualize neovascularization of atherosclerot‐ ic plaques [21-24]. In addition, Vorpahl et al demonstrated that small black holes in atheroma‐ tous plaques observed by OCT were in good agreement with the pathohistological evidence of intra-plaque neoangiogenesis formation in an autopsy case [25]. We recently assessed the rela‐ tionship between intra-plaque microchannel structures identified by OCT, probably repre‐ senting neovascularization, and plaque vulnerability in patients with coronary artery disease [21]. In this study, microchannel was defined as a no-signal tubuloluminal structure that was present on at least 3 consecutive OCT cross-sections in pull-back images. As a result, micro‐ channels were seen in 38% of culprit plaques, and plaques with microchannels displayed the characteristics of vulnerability such as positive remodeling and thin fibrous caps compared with plaques without these structures. Of note, the presence of increased microchannel counts was correlated with a greater frequency of thin-capped fibroatheroma (TCFA) (Figure 2). More recently, in larger study population (356 plaques in 117 patients), Tian et al investigated the clinical significance of intra-plaque neovascularization in culprit lesions and no-culprit le‐ sions of unstable angina pectoris (UAP) and in lesions of stable angina pectoris (SAP) using OCT [22]. Intra-plaque neovascularization was found in 35% of UAP culprit lesions, in 34% of UAP non-culprit lesions, and in 28% of SAP lesions, with no significant difference. Among UAP culprit lesions, plaques with neovessel had thinner fibrous cap thickness (56±20 µm vs. 75±30 µm, p<0.001) and significantly higher incidence of TCFA (81% vs. 47%, p=0.002) com‐ pared with those without neovessel. In addition, plaque burden was significantly bigger in UAP culprit lesions with neovascularization (79.8±7.9% vs. 72.8±10.7%, p=0.024). In terms of the non-culprit lesions of UAP patients and lesions of SAP patients, however, no significant difference in plaque characteristics was observed, regardless of the presence or absence of neo‐ vascularization. Interestingly, Kato et al reported that although the overall prevalence of mi‐ crochannel in non-culprit lesions was not significantly different between ACS and non-ACS patients (64.7% versus 55.2%, respectively, P=0.647), the closest distance from the lumen to mi‐ crochannel was shorter in ACS subjects than in non-ACS (104.6±67.0 µm versus 198.3±133.0 µm, p=0.027) [23]. The authors speculated that because neovascular networks expand from the adventitia into the intima as disease progresses [26], plaques with neovascularization located closer to the lumen might represent an advanced stage of atherosclerosis. Furthermore, Ue‐ mura et al revealed that microchannel structure in non-culprit plaques (defined as percent di‐ ameter stenosis of < 50%) identified by OCT is a predictor of subsequent plaque progression in patients with coronary artery disease [24].

layers of the vessel wall, and becomes major source of nutrients. Vasa vasorum neovascula‐ rization in early atherosclerosis is associated with inflammatory cell infiltration and lipid deposition, leading to plaque progression [10]. Furthermore, intraplaque hemorrhage from microvessels contributes to expansion of the necrotic core through the accumulation of free cholesterol from erythrocyte membranes. Several human pathologic studies have demon‐ strated that plaque neovascularization is pronounced among patients with unstable coro‐ nary syndromes and that its presence may be a marker of plaque instability and plaque rupture [4, 5, 11]. Therefore, investigations of imaging methods with the ability to visualize

Several imaging modalities such as micro-computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound have emerged as potential techniques for imaging neoves‐ sels in atherosclerotic plaques. Micro-CT provides high-resolution images of coronary vasa vasorum neovascularization and insight into their structure and function in animal models [12, 13]. Winter et al have reported that molecular MRI with αvβ3-targeted, paramagnetic nanoparticles can detect plaque neovessels in atherosclerotic rabbit model [14]. In addition, more recently, Sirol et al have demonstrated how gadofluorine M-enhanced MRI can accu‐ rately identify plaque neovascularization in an animal model of atherosclerosis with good histological correlation [15]. Thus, even though the results from these techniques are prom‐ ising, further studies are needed for clinical application in humans. Intravascular ultrasound (IVUS) has the potential to detect flow within the plaque and subsequently evaluate func‐ tional neovessels. The development of IVUS-based imaging has recently demonstrated the preliminary data imaging neovascularization in coronary plaques in vivo after intravascular injection of microbubbles [16,17], but further investigations will be required to show the fea‐

OCT has been proposed as a high-resolution imaging modality that can identify micro-struc‐ tures in atherosclerotic plaques [8, 18, 19]. The superb high-resolution of OCT may offer an op‐ portunity of studying the spatial distribution of plaque neovascularization in vivo (Figure 1) [20]. In fact, it has been shown that OCT is able to visualize neovascularization of atherosclerot‐ ic plaques [21-24]. In addition, Vorpahl et al demonstrated that small black holes in atheroma‐ tous plaques observed by OCT were in good agreement with the pathohistological evidence of intra-plaque neoangiogenesis formation in an autopsy case [25]. We recently assessed the rela‐ tionship between intra-plaque microchannel structures identified by OCT, probably repre‐ senting neovascularization, and plaque vulnerability in patients with coronary artery disease [21]. In this study, microchannel was defined as a no-signal tubuloluminal structure that was present on at least 3 consecutive OCT cross-sections in pull-back images. As a result, micro‐ channels were seen in 38% of culprit plaques, and plaques with microchannels displayed the

neovascularization would appear worthwhile.

104 Optical Coherence Tomography

sibility of this method for routine clinical use.

**4. Plaque neovascularization by OCT**

**3. Potential imaging modalities of neovascularization**

**Figure 1.** OCT (M2 system) images of plaque neovessels. Microvessels in the outer plaque (A) near the adventitia and (B) within the thickened intima can appear as signal-poor voids (white arrows) that are sharply delineated.

homogeneously in the early phase, neointima inside the BMS ≥ 5 years after implantation was characterized by marked signal attenuation and a diffuse border, suggesting lipid-laden intima. Its frequency was 67% and lipid-laden intima was not observed in the early phase. TCFA-like intima was also found in 29% of the patients in the late phase. Intimal disruption and thrombus were observed more frequently in the late phase as compared with the early phase (38% vs. 0% and 52% vs. 5%, respectively; p < 0.05). Notably, although there was no significant difference in terms of the incidence of peristent neovascularization (Figure 3A) between the 2 phases (81% vs. 60%, p=0.14), intraintima neovascularization (Figure 3B) was seen more frequently in the late phase than in the early phase (62% vs. 0%, p < 0.01) and in segments with lipid-laden intima than those in without lipid-laden intima (79% vs. 29%, p=0.026). Moreover, Habara et al evaluated the difference of tissue characteristics between early (within the first year) and very late (> 5 years, without restenosis within the first years) restenostic lesions after BMS implantation by using OCT [39]. There was a significant differ‐ ence in the morphological characteristics of restenostic tissue between very late ISR (charac‐ terized by heterogeneous intima) and early ISR (characterized by homogeneous intima). Intraintima microvessels were observed only in the very late ISR group (16.3% vs. 0%, p=0.01). Thus, expansion of neovascularization from persistent to intraintimal area with time may contribute to atherosclerosis progression of neointima, as well as intra-plaque neovas‐

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107

**Figure 3.** Neovascularization within neointima inside the implanted stent. (A) OCT (M2 system) image of peristent mi‐ crovessels (arrows) demonstrating no-signal small vesicular and tubular structures locating around the struts. (B) OCT (M2 system) image of intraintima microvessels (arrows) showing small black holes locating near the vessel lumen with‐

cularization of nonstent segments in native coronary arteries.

in the neotintimal tissue.

**Figure 2.** Comparison of frequency of TCFA according to number of microchannels. When categorized into 3 groups according to number of microchannels, the frequency of TCFA (21% in group with 0, 40% in group with 1, and 64% in group with ≥ 2; p < 0.003 for all) was significantly different. Reproduced with permission from [21].

#### **5. Neovascularization inside the implanted stent by OCT**

Although neovascularization within the neointima after stent implantation has been already reported in histopathologic studies [27, 28], Regar et al first reported in 2005 that OCT has an ability to visualize microvessels within the neointima inside the stents in a living human [29]. Later the presence of neovascularization in the stent restenosis was noted by Gonzalo et al [30]. However, the role of microvessels in restenotic tissue behavior has been unknown. More recently, Kim et al evaluated the characteristics of in-stent restenosis (ISR) lesions with microvessels detected by OCT [31]. Microvessels were detected in 21 (27%) of 78 ISR lesions. At the minimum lumen area site, the neointimal area (5.4 ± 1.7 mm2 vs. 4.2 ± 2.1 mm2 , p=0.024) and percent neointimal area (79±12% vs. 67±16%, p=0.001) were significantly great‐ er in ISR lesions with microvessels. These results suggest that microvessels within the neoin‐ tima might be associated with restenosis by the excessive neointimal growth following stent implantation.

Furthermore, it has been shown that neointima in both BMS and DES can transform into atherosclerotic tissue with time although it occurs earlier in DES than BMS and that neoa‐ throsclerosis progression inside the implanted stents may be associated with very late coro‐ nary events such as very late stent thrombosis after BMS and DES implantation [28, 32-40]. Using OCT, Takano et al examined the differences in neointima between early phase (< 6 months) and late phase (≥ 5 years) [35]. When compared with normal neointima proliferated homogeneously in the early phase, neointima inside the BMS ≥ 5 years after implantation was characterized by marked signal attenuation and a diffuse border, suggesting lipid-laden intima. Its frequency was 67% and lipid-laden intima was not observed in the early phase. TCFA-like intima was also found in 29% of the patients in the late phase. Intimal disruption and thrombus were observed more frequently in the late phase as compared with the early phase (38% vs. 0% and 52% vs. 5%, respectively; p < 0.05). Notably, although there was no significant difference in terms of the incidence of peristent neovascularization (Figure 3A) between the 2 phases (81% vs. 60%, p=0.14), intraintima neovascularization (Figure 3B) was seen more frequently in the late phase than in the early phase (62% vs. 0%, p < 0.01) and in segments with lipid-laden intima than those in without lipid-laden intima (79% vs. 29%, p=0.026). Moreover, Habara et al evaluated the difference of tissue characteristics between early (within the first year) and very late (> 5 years, without restenosis within the first years) restenostic lesions after BMS implantation by using OCT [39]. There was a significant differ‐ ence in the morphological characteristics of restenostic tissue between very late ISR (charac‐ terized by heterogeneous intima) and early ISR (characterized by homogeneous intima). Intraintima microvessels were observed only in the very late ISR group (16.3% vs. 0%, p=0.01). Thus, expansion of neovascularization from persistent to intraintimal area with time may contribute to atherosclerosis progression of neointima, as well as intra-plaque neovas‐ cularization of nonstent segments in native coronary arteries.

**Figure 2.** Comparison of frequency of TCFA according to number of microchannels. When categorized into 3 groups according to number of microchannels, the frequency of TCFA (21% in group with 0, 40% in group with 1, and 64% in

Although neovascularization within the neointima after stent implantation has been already reported in histopathologic studies [27, 28], Regar et al first reported in 2005 that OCT has an ability to visualize microvessels within the neointima inside the stents in a living human [29]. Later the presence of neovascularization in the stent restenosis was noted by Gonzalo et al [30]. However, the role of microvessels in restenotic tissue behavior has been unknown. More recently, Kim et al evaluated the characteristics of in-stent restenosis (ISR) lesions with microvessels detected by OCT [31]. Microvessels were detected in 21 (27%) of 78 ISR lesions.

p=0.024) and percent neointimal area (79±12% vs. 67±16%, p=0.001) were significantly great‐ er in ISR lesions with microvessels. These results suggest that microvessels within the neoin‐ tima might be associated with restenosis by the excessive neointimal growth following stent

Furthermore, it has been shown that neointima in both BMS and DES can transform into atherosclerotic tissue with time although it occurs earlier in DES than BMS and that neoa‐ throsclerosis progression inside the implanted stents may be associated with very late coro‐ nary events such as very late stent thrombosis after BMS and DES implantation [28, 32-40]. Using OCT, Takano et al examined the differences in neointima between early phase (< 6 months) and late phase (≥ 5 years) [35]. When compared with normal neointima proliferated

vs. 4.2 ± 2.1 mm2

,

group with ≥ 2; p < 0.003 for all) was significantly different. Reproduced with permission from [21].

**5. Neovascularization inside the implanted stent by OCT**

At the minimum lumen area site, the neointimal area (5.4 ± 1.7 mm2

implantation.

106 Optical Coherence Tomography

**Figure 3.** Neovascularization within neointima inside the implanted stent. (A) OCT (M2 system) image of peristent mi‐ crovessels (arrows) demonstrating no-signal small vesicular and tubular structures locating around the struts. (B) OCT (M2 system) image of intraintima microvessels (arrows) showing small black holes locating near the vessel lumen with‐ in the neotintimal tissue.

#### **6. Future perspectives (neovascularization as a therapeutic target for plaque stabilization)**

Moreover, a newer-generation Frequency-domain OCT (FD-OCT; C7 system, LightLab Imaging) has recently been developed to overcome many of the technical limitations of TD-OCT system by imaging at much higher frame rates (100 frame/s), a larger scan diameter (10 mm) and a faster image acquisition rate (20 mm/s) without loss of image quality, and unlike TD-OCT, this technology does not require proximal balloon occlusion [48]. The imaging catheter of FD-OCT, which is designed for rapid exchange delivery, has a 2.7-Fr crossing profile and can be delivered over a 0.014-inch guidewire through a 6-Fr or larger guide cath‐ eter. Intracoronary injection of contrast media via the guide catheter (3 to 4 ml/s; 2-3 s) can achieve effective clearing of blood for the FD-OCT imaging. In combination with a short, nonocclusive flush and a faster pullback speed, the FD-OCT enables imaging of longer seg‐ ments of coronary arteries without significant ischemia and motion artifact [49]. Thus, we would be able to more precisely and easily assess not only culprit but also nonculprit lesion

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109

First, because the penetration depth of OCT is relatively shallow (<2 mm), and OCT light signals are limited behind the lipid component or red thrombus, previous OCT studies may underestimate the presence of neovascularization. Second, neovessel size has been inconsis‐ tently defined by a wide range because it is unknown whether there is a threshold for the size of these vessels within the intima [50]. Finally, a direct comparison of OCT-derived mi‐ crochannels with histology has not been done to date. Therefore, histological studies that properly validate these structures observed with in vivo OCT imaging are mandatory in the

OCT has the potential to directly visualize neovascularization of atherosclerotic plaques in vivo. Microchannel structure in coronary plaques identified by OCT could be a marker of plaque vulnerability to improve patient risk stratification and a therapeutic target for plaque

The authors thank Takashi Kubo, MD; Kenichi Komukai, MD; Yasushi Ino, MD; Takashi Ta‐ nimoto, MD; Kohei Ishibashi, MD; Manabu Kashiwagi, MD; Yuichi Ozaki, MD; Kunihiro Shimamura, MD; Makoto Orii, MD; Yasutsugu Shiono, MD for assitance with OCT image

morphologies in coronary artery disease by use of FD-OCT.

**7. Limitations**

near future.

stabilization.

**Acknowledgement**

acquisition and analysis.

**8. Conclusions**

For all cardiologists, stabilizing vulnerable plaques remains a major concern. Previous clini‐ cal trials have demonstrated that lipid-lowering therapy by statins stabilizes vulnerable pla‐ ques, thereby preventing cardiac events. Experimental studies have also shown that antiatherosclerotic therapies can reduce plaque neovascularization [41-43] and that the inhibition of plaque neovascularization reduces progression of advanced atherosclerosis [41, 42]. Therefore, monitoring treatment effects of anti-atherosclerotic drugs using reliable sur‐ rogate markers may be useful to appropriately manage the patients. The thickness of fibrous cap in coronary plaque is a major determinant of plaque destabilization [44]. We recently re‐ ported that statins increased the fibrous cap thickness of plaques as assessed by OCT, indi‐ cating plaque stabilization [45, 46]. More recently, Tian et al investigated whether there was a difference in the effects of statin therapy between lesions with and without neovasculari‐ zation [47]. As a result, despite a comparable reduction in serum cholesterol levels, the fi‐ brous cap thickening was smaller in lesions with neovascularization than those without neovascularization after 6 and 12 months of statin treatment, which suggests that a more ag‐ gressive anti-atherosclerotic therapy may be required in patients with plaque with neovas‐ cularization. Thus, OCT allows us to monitor the response to anti-atherosclerotic therapies such as statins, and micro-channels in plaques identified by OCT could become a therapeu‐ tic target for plaque stabilization as important as the thickness of fibrous cap (Figure 4).

**Figure 4.** Plaque stabilization and elimination of neovascularization by statin treatment. (A) OCT (M2 system) demon‐ strates lipid-rich plaque covered by thin fibrous cap of 60 μm (thin-capped fibroatheroma) and microvessels at the shoulder region of the plaque (dotted circle). (B) Six months after statin treatment, the minimum fibrous cap thickness (FCT) increased from 60 μm to 170 μm and microvessels disappeared.

Moreover, a newer-generation Frequency-domain OCT (FD-OCT; C7 system, LightLab Imaging) has recently been developed to overcome many of the technical limitations of TD-OCT system by imaging at much higher frame rates (100 frame/s), a larger scan diameter (10 mm) and a faster image acquisition rate (20 mm/s) without loss of image quality, and unlike TD-OCT, this technology does not require proximal balloon occlusion [48]. The imaging catheter of FD-OCT, which is designed for rapid exchange delivery, has a 2.7-Fr crossing profile and can be delivered over a 0.014-inch guidewire through a 6-Fr or larger guide cath‐ eter. Intracoronary injection of contrast media via the guide catheter (3 to 4 ml/s; 2-3 s) can achieve effective clearing of blood for the FD-OCT imaging. In combination with a short, nonocclusive flush and a faster pullback speed, the FD-OCT enables imaging of longer seg‐ ments of coronary arteries without significant ischemia and motion artifact [49]. Thus, we would be able to more precisely and easily assess not only culprit but also nonculprit lesion morphologies in coronary artery disease by use of FD-OCT.

#### **7. Limitations**

**6. Future perspectives (neovascularization as a therapeutic target for**

For all cardiologists, stabilizing vulnerable plaques remains a major concern. Previous clini‐ cal trials have demonstrated that lipid-lowering therapy by statins stabilizes vulnerable pla‐ ques, thereby preventing cardiac events. Experimental studies have also shown that antiatherosclerotic therapies can reduce plaque neovascularization [41-43] and that the inhibition of plaque neovascularization reduces progression of advanced atherosclerosis [41, 42]. Therefore, monitoring treatment effects of anti-atherosclerotic drugs using reliable sur‐ rogate markers may be useful to appropriately manage the patients. The thickness of fibrous cap in coronary plaque is a major determinant of plaque destabilization [44]. We recently re‐ ported that statins increased the fibrous cap thickness of plaques as assessed by OCT, indi‐ cating plaque stabilization [45, 46]. More recently, Tian et al investigated whether there was a difference in the effects of statin therapy between lesions with and without neovasculari‐ zation [47]. As a result, despite a comparable reduction in serum cholesterol levels, the fi‐ brous cap thickening was smaller in lesions with neovascularization than those without neovascularization after 6 and 12 months of statin treatment, which suggests that a more ag‐ gressive anti-atherosclerotic therapy may be required in patients with plaque with neovas‐ cularization. Thus, OCT allows us to monitor the response to anti-atherosclerotic therapies such as statins, and micro-channels in plaques identified by OCT could become a therapeu‐ tic target for plaque stabilization as important as the thickness of fibrous cap (Figure 4).

**Figure 4.** Plaque stabilization and elimination of neovascularization by statin treatment. (A) OCT (M2 system) demon‐ strates lipid-rich plaque covered by thin fibrous cap of 60 μm (thin-capped fibroatheroma) and microvessels at the shoulder region of the plaque (dotted circle). (B) Six months after statin treatment, the minimum fibrous cap thickness

(FCT) increased from 60 μm to 170 μm and microvessels disappeared.

**plaque stabilization)**

108 Optical Coherence Tomography

First, because the penetration depth of OCT is relatively shallow (<2 mm), and OCT light signals are limited behind the lipid component or red thrombus, previous OCT studies may underestimate the presence of neovascularization. Second, neovessel size has been inconsis‐ tently defined by a wide range because it is unknown whether there is a threshold for the size of these vessels within the intima [50]. Finally, a direct comparison of OCT-derived mi‐ crochannels with histology has not been done to date. Therefore, histological studies that properly validate these structures observed with in vivo OCT imaging are mandatory in the near future.

#### **8. Conclusions**

OCT has the potential to directly visualize neovascularization of atherosclerotic plaques in vivo. Microchannel structure in coronary plaques identified by OCT could be a marker of plaque vulnerability to improve patient risk stratification and a therapeutic target for plaque stabilization.

#### **Acknowledgement**

The authors thank Takashi Kubo, MD; Kenichi Komukai, MD; Yasushi Ino, MD; Takashi Ta‐ nimoto, MD; Kohei Ishibashi, MD; Manabu Kashiwagi, MD; Yuichi Ozaki, MD; Kunihiro Shimamura, MD; Makoto Orii, MD; Yasutsugu Shiono, MD for assitance with OCT image acquisition and analysis.

#### **Author details**

Hironori Kitabata and Takashi Akasaka

Wakayama Medical University, Japan

#### **References**

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JF, Guagliumi G, Holm NR, Honda Y, Ikeno F, Kawasaki M, Kochman J, Koltowski L, Kubo T, Kume T, Kyono H, Lam CC, Lamouche G, Lee DP, Leon MB, Maehara A, Manfrini O, Mintz GS, Mizuno K, Morel MA, Nadkarni S, Okura H, Otake H, Pietra‐ sik A, Prati F, Räber L, Radu MD, Rieber J, Riga M, Rollins A, Rosenberg M, Sirbu V, Serruys PW, Shimada K, Shinke T, Shite J, Siegel E, Sonoda S, Suter M, Takarada S, Tanaka A, Terashima M, Thim T, Uemura S, Ughi GJ, van Beusekom HM, van der Steen AF, van Es GA, van Soest G, Virmani R, Waxman S, Weissman NJ, Weisz G; International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT).Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation. J Am Coll Cardiol 2012;59(12):1058-1072.

implantation: intracoronary optical coherence tomography examination. Am Heart J

[41] Moulton KS, Heller E, Konerding MA, Flynn E, Palinski W, Folkman J. Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque

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[44] Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons from sudden cor‐ onary death: a comprehensive morphological classification scheme for atherosclerot‐

[45] Takarada S, Imanishi T, Kubo T, Tanimoto T, Kitabata H, Nakamura N, Tanaka A, Mizukoshi M, Akasaka T. Effect of statin therapy on coronary fibrous-cap thickness in patients with acute coronary syndrome: Assessment by optical coherence tomog‐

[46] Takarada S, Imanishi T, Ishibashi K, Tanimoto T, Komukai K, Ino Y, Kitabata H, Ku‐ bo T, Tanaka A, Kimura K, Mizukoshi M, Akasaka T. The effect of lipid and inflam‐ matory profiles on the morphological changes of lipid-rich plaques in patients with non-ST-segment elevated acute coronary syndrome: follow-up study by optical co‐ herence tomography and intravascular ultrasound. J Am Coll Cardiol Intv 2010;3(7):

[47] Tian J, Hou J, Xing L, Kim SJ, Yonetsu T, Kato K, Lee H, Zhang S, Yu B, Jang IK. Does neovascularization predict response to statin therapy? Optical coherence tomogra‐

[48] Barlis P, Schmitt JM: Current and future developments in intracoronary optical co‐

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114 Optical Coherence Tomography

415-418.

766-772.

**Chapter 6**

**Optical Coherence Tomography (OCT): A New Imaging**

One of the mechanisms underlying acute stroke is the disruption of atherosclerotic plaques in major cerebral vessels, including the carotid arteries. However, visualizing precise arterial wall changes is sometimes difficult using conventional imaging techniques such as angiography, magnetic resonance imaging (MRI) or duplex ultrasonography. In particular, intraluminal thrombus is difficult to detect clearly during catheter interventions such as carotid artery stenting (CAS), even with utilization of intravascular ultrasonography (IVUS) [1,2]. When visualization of the carotid wall changes is possible during CAS, especially before and after angioplasty and stenting, it then becomes possible be to select appropriate devices and methods of angioplasty and cerebral protection based on better anatomical information.

Intravascular optical coherence tomography (OCT) has recently been proposed as a highresolution imaging tool for plaque characterization in the coronary arteries. OCT is a noncontact, light-based imaging method utilizing newly developed fiber-optic technology (Fig. 1). The typical OCT image has an axial resolution of 10 µm, approximately 10 times higher than that of any other clinically available diagnostic imaging modality such as IVUS with a resolution of 80 µm [3]. Therefore, despite the need for removing blood from the field of view, in vivo application of OCT has been reported useful in the coronary arteries [4-7]. For example, Jang IK et al reported that intracoronary OCT identified most architectural features detected by IVUS and provided additional detailed structural information [4]. Kawasaki M et al claimed that OCT had the best potential for tissue characterization of coronary plaques, within the

> © 2013 Yoshimura et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2013 Yoshimura et al.; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**Tool During Carotid Artery Stenting**

Shinichi Yoshimura, Masanori Kawasaki,

Kazuhiko Nishigaki, Shinya Minatoguchi and

Additional information is available at the end of the chapter

Kiyofumi Yamada, Arihiro Hattori,

http://dx.doi.org/10.5772/53962

Toru Iwama

**1. Introduction**

### **Optical Coherence Tomography (OCT): A New Imaging Tool During Carotid Artery Stenting**

Shinichi Yoshimura, Masanori Kawasaki, Kiyofumi Yamada, Arihiro Hattori, Kazuhiko Nishigaki, Shinya Minatoguchi and Toru Iwama

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/53962

**1. Introduction**

One of the mechanisms underlying acute stroke is the disruption of atherosclerotic plaques in major cerebral vessels, including the carotid arteries. However, visualizing precise arterial wall changes is sometimes difficult using conventional imaging techniques such as angiography, magnetic resonance imaging (MRI) or duplex ultrasonography. In particular, intraluminal thrombus is difficult to detect clearly during catheter interventions such as carotid artery stenting (CAS), even with utilization of intravascular ultrasonography (IVUS) [1,2]. When visualization of the carotid wall changes is possible during CAS, especially before and after angioplasty and stenting, it then becomes possible be to select appropriate devices and methods of angioplasty and cerebral protection based on better anatomical information.

Intravascular optical coherence tomography (OCT) has recently been proposed as a highresolution imaging tool for plaque characterization in the coronary arteries. OCT is a noncontact, light-based imaging method utilizing newly developed fiber-optic technology (Fig. 1). The typical OCT image has an axial resolution of 10 µm, approximately 10 times higher than that of any other clinically available diagnostic imaging modality such as IVUS with a resolution of 80 µm [3]. Therefore, despite the need for removing blood from the field of view, in vivo application of OCT has been reported useful in the coronary arteries [4-7]. For example, Jang IK et al reported that intracoronary OCT identified most architectural features detected by IVUS and provided additional detailed structural information [4]. Kawasaki M et al claimed that OCT had the best potential for tissue characterization of coronary plaques, within the

© 2013 Yoshimura et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 Yoshimura et al.; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

penetration depth of OCT, in a comparative study with IVUS [7]. Based on these results, we speculated that intravascular OCT would also be useful for the other vessels. Our use of OCT for human carotid arteries was approved by our institutional review board (No. 21-108), and recently registered on the Internet (University Hospital Medical Information Network: UMIN 000002808).

**2. First application of OCT for the human carotid artery**

confirmed by histological analysis of the surgical specimen.

with OCT findings. This study was reported previously [8].

Our group first applied intravascular OCT in a patient with a large thrombus in the carotid artery [8]. An 83-year old male admitted due to motor weakness of the left hand. Diffusion weighted MRI showed multiple high intensity spots in the territory of the right middle cerebral artery, and magnetic resonance angiography (MRA) revealed significant stenosis at the origin of the right internal carotid artery (Fig. 2A). Because of an apparent change in plaque shape on the angiogram just before CAS (Fig. 2B), further examinations such as IVUS and OCT were performed. After IVUS examination (Fig. 2D), both the common carotid and external carotid arteries were occluded by an occlusion balloon system prepared for CAS. Then, the stenotic site was imaged by OCT (M2 OCT Imaging system, LightLab Imaging, Inc., Westford, Massachusetts) from the distal section at 1mm/sec using a built-in pull-back system with continuous injection of saline through the guiding catheter to remove blood from the field of view. Intraluminal thrombus was clearly demonstrated by OCT (Fig. 2C), and carotid endar‐ terectomy was performed instead of stenting to avoid distal migration of the thrombus during the revascularization procedure. The carotid artery specimen obtained by endarterectomy showed a soft plaque with a large intraluminal thrombus, which correlated with OCT findings performed preoperatively (Fig. 2E,F). This was the first report of a clinical application of the OCT in the carotid artery, and the intraluminal thrombus detected by OCT was successfully

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**Figure 2.** An intraluminal thrombus in the carotid artery demonstrated by OCT and confirmed by pathological analysis.A: initial magnetic resonance angiography revealed severe stenosis of the internal carotid artery (ICA) and high-intensity plaque. B: the carotid angiogram showed ICA stenosis and enlargement of an intraluminal protrusion in the ICA. C: cross sections by OCT demonstrated an intraluminal thrombus with shadowing in the ICA. D: cross sections by intravascular ultrasonography showed only eccentric and low-echoic plaque in the ICA.E: macroscopic view of a surgical specimen showing an intraluminal thrombus formed at the ruptured site of the plaque. F: pathological analysis with hematoxylineosin staining confirmed soft plaque with intraplaque hemorrhage and an intraluminal red thrombus, which correlated

**Figure 1.** Images of an optical coherence tomography (OCT) system and an imagewire. This is the first generation of OCT analyzer (M2 OCT Imaging system, LightLab Imaging, Inc., Westford, Massachusetts, A), which was used for our clinical studies. An imagewire is schematically demonstrated to show its scanning capabilities during the target artery occlusion using an occlusion balloon (B).

#### **2. First application of OCT for the human carotid artery**

penetration depth of OCT, in a comparative study with IVUS [7]. Based on these results, we speculated that intravascular OCT would also be useful for the other vessels. Our use of OCT for human carotid arteries was approved by our institutional review board (No. 21-108), and recently registered on the Internet (University Hospital Medical Information Network: UMIN

**Figure 1.** Images of an optical coherence tomography (OCT) system and an imagewire. This is the first generation of OCT analyzer (M2 OCT Imaging system, LightLab Imaging, Inc., Westford, Massachusetts, A), which was used for our clinical studies. An imagewire is schematically demonstrated to show its scanning capabilities during the target artery

occlusion using an occlusion balloon (B).

**A**

000002808).

118 Optical Coherence Tomography

Our group first applied intravascular OCT in a patient with a large thrombus in the carotid artery [8]. An 83-year old male admitted due to motor weakness of the left hand. Diffusion weighted MRI showed multiple high intensity spots in the territory of the right middle cerebral artery, and magnetic resonance angiography (MRA) revealed significant stenosis at the origin of the right internal carotid artery (Fig. 2A). Because of an apparent change in plaque shape on the angiogram just before CAS (Fig. 2B), further examinations such as IVUS and OCT were performed. After IVUS examination (Fig. 2D), both the common carotid and external carotid arteries were occluded by an occlusion balloon system prepared for CAS. Then, the stenotic site was imaged by OCT (M2 OCT Imaging system, LightLab Imaging, Inc., Westford, Massachusetts) from the distal section at 1mm/sec using a built-in pull-back system with continuous injection of saline through the guiding catheter to remove blood from the field of view. Intraluminal thrombus was clearly demonstrated by OCT (Fig. 2C), and carotid endar‐ terectomy was performed instead of stenting to avoid distal migration of the thrombus during the revascularization procedure. The carotid artery specimen obtained by endarterectomy showed a soft plaque with a large intraluminal thrombus, which correlated with OCT findings performed preoperatively (Fig. 2E,F). This was the first report of a clinical application of the OCT in the carotid artery, and the intraluminal thrombus detected by OCT was successfully confirmed by histological analysis of the surgical specimen.

**Figure 2.** An intraluminal thrombus in the carotid artery demonstrated by OCT and confirmed by pathological analysis.A: initial magnetic resonance angiography revealed severe stenosis of the internal carotid artery (ICA) and high-intensity plaque. B: the carotid angiogram showed ICA stenosis and enlargement of an intraluminal protrusion in the ICA. C: cross sections by OCT demonstrated an intraluminal thrombus with shadowing in the ICA. D: cross sections by intravascular ultrasonography showed only eccentric and low-echoic plaque in the ICA.E: macroscopic view of a surgical specimen showing an intraluminal thrombus formed at the ruptured site of the plaque. F: pathological analysis with hematoxylineosin staining confirmed soft plaque with intraplaque hemorrhage and an intraluminal red thrombus, which correlated with OCT findings. This study was reported previously [8].

It has been reported that neither angiography nor IVUS can reliably demonstrate the presence of a thrombus [1]. In this patient, a thrombus in the carotid artery was clearly demonstrated by preoperative OCT. Due to the size of thrombus the information provided by OCT which altered therapy, possible embolism and its consequences of hemiparesis or speech disturbance was averted.

Kume et al reported that OCT could differentiate between red and white coronary arterial thrombi by post mortem, ex vivo experiments [9]. Meng et al reported on the feasibility of OCT for the detection of in vivo acute thrombosis in the carotid artery using an animal model [10]. They also reported an excellent correlation between OCT images and histology regarding thrombus length and location. OCT images of red thrombi are characterized as highly backscattered protrusions with signal-free shadowing. A red thrombus consists mainly of red blood cells, causing scatter and attenuation of OCT signal intensity from the inner surface of the thrombus to the vessel wall. In our patient, the protruded mass in the ICA (Fig. 2B) was diagnosed as a red thrombus by OCT (Fig. 2C) because of signal attenuation behind the mass, and pathologically confirmed thereafter (Fig. 2E,F).

#### **3. Comparison of OCT with IVUS during stenting**

Next, this group applied OCT for the carotid artery during stenting as a clinical study. In this study, we evaluated the ability of OCT to visualize structures of the carotid artery wall when compared with IVUS. We reported typical images of this preliminary OCT application to human carotid arteries during CAS [11]. OCT was performed on 20 plaques of 17 patients

**Figure 3.** Representative images of carotid plaque with fibrous cap disruption from a symptomatic patient with right ICA stenosis prior to carotid artery stenting (CAS). A: an image from OCT shows fibrous cap disruption as a discontinu‐ ous fibrous cap and cavity formation (arrow). B: IVUS was not able to detect the fibrous cap disruption. The bar in both A and B equals 2 mm. This study was reported previously [11].

**Figure 4.** Tissue Protrusion. Representative images of carotid plaque protrusion in a symptomatic patient with left ICA stenosis after carotid artery stenting (CAS). Plaque protrusion is considered to be one source for the embolic complica‐ tion after CAS. Plaque protrusion from stent struts just after stent deployment was clearly demonstrated by OCT, but was overlooked by IVUS. A: Carotid angiogram demonstrating the plaque protrusion after stent placement ( arrow). B: OCT demonstrates tissue protrusion from spaces between stent struts (white arrows). C, D: IVUS with and without ChromaFlo (Eagle Eye Gold, Volcano Therapeutics, Rancho Cordova, California) was unable to see plaque protrusions.

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The bar in B, C, and D equals 2 mm. This study was reported previously [11].

It has been reported that neither angiography nor IVUS can reliably demonstrate the presence of a thrombus [1]. In this patient, a thrombus in the carotid artery was clearly demonstrated by preoperative OCT. Due to the size of thrombus the information provided by OCT which altered therapy, possible embolism and its consequences of hemiparesis or speech disturbance

Kume et al reported that OCT could differentiate between red and white coronary arterial thrombi by post mortem, ex vivo experiments [9]. Meng et al reported on the feasibility of OCT for the detection of in vivo acute thrombosis in the carotid artery using an animal model [10]. They also reported an excellent correlation between OCT images and histology regarding thrombus length and location. OCT images of red thrombi are characterized as highly backscattered protrusions with signal-free shadowing. A red thrombus consists mainly of red blood cells, causing scatter and attenuation of OCT signal intensity from the inner surface of the thrombus to the vessel wall. In our patient, the protruded mass in the ICA (Fig. 2B) was diagnosed as a red thrombus by OCT (Fig. 2C) because of signal attenuation behind the mass,

Next, this group applied OCT for the carotid artery during stenting as a clinical study. In this study, we evaluated the ability of OCT to visualize structures of the carotid artery wall when compared with IVUS. We reported typical images of this preliminary OCT application to human carotid arteries during CAS [11]. OCT was performed on 20 plaques of 17 patients

**Figure 3.** Representative images of carotid plaque with fibrous cap disruption from a symptomatic patient with right ICA stenosis prior to carotid artery stenting (CAS). A: an image from OCT shows fibrous cap disruption as a discontinu‐ ous fibrous cap and cavity formation (arrow). B: IVUS was not able to detect the fibrous cap disruption. The bar in both

was averted.

120 Optical Coherence Tomography

and pathologically confirmed thereafter (Fig. 2E,F).

A and B equals 2 mm. This study was reported previously [11].

**3. Comparison of OCT with IVUS during stenting**

**Figure 4.** Tissue Protrusion. Representative images of carotid plaque protrusion in a symptomatic patient with left ICA stenosis after carotid artery stenting (CAS). Plaque protrusion is considered to be one source for the embolic complica‐ tion after CAS. Plaque protrusion from stent struts just after stent deployment was clearly demonstrated by OCT, but was overlooked by IVUS. A: Carotid angiogram demonstrating the plaque protrusion after stent placement ( arrow). B: OCT demonstrates tissue protrusion from spaces between stent struts (white arrows). C, D: IVUS with and without ChromaFlo (Eagle Eye Gold, Volcano Therapeutics, Rancho Cordova, California) was unable to see plaque protrusions. The bar in B, C, and D equals 2 mm. This study was reported previously [11].

during CAS, under a proximal cerebral protection method. In addition to intraluminal thrombus, fibrous cap disruption (Fig. 3) and plaque protrusion after stenting (Fig. 4) were easily detected by OCT. There were no technical or neurological complications in this series. OCT could best visualize the lateral side of lumen pathology (intraluminal thrombus or fibrous cap disruption) with a high resolution of 10 um, whereas IVUS, MRI, or computed tomography allowed assessment of the entire arterial wall, albeit with lesser resolution. OCT and IVUS thus complement each other and may aid in discriminating plaques that are eligible for CAS.

calcification, lipid-rich necrotic core, ulceration, and plaque protrusion after stent placement between groups. *Interobserver* and intraobserver variability with OCT diagnosis was excellent

Male, n (%) 14 (82.4) 15 (88.2) "/>0.99 Age, yr 72 ± 10 68 ± 10 0.19 Degree of stenosis, % 84 ± 12 79 ± 7 0.26

Thrombus 13 (76.5) 2 (11.8) <0.001 Neovascularization 10 (58.8) 3 (17.6) 0.03 Ulceration 3 (17.6) 0 (0) 0.23 Calcification 7 (41.2) 6 (35.3) "/>0.99 Lipid-rich component 16 (94.1) 12 (70.6) 0.17 Plaque protrusion 4 (23.5) 2 (11.8) 0.66

The major limitations of OCT are interference by blood flow and the degree of tissue penetra‐ tion. To obtain a bloodless field of view, a proximal protection method which uses occlusion balloons for the common and external carotid arteries is required for the application of OCT in the cervical carotid artery [8, 11, 12]. The scanning length of OCT was 3.25 to 3.4 mm in normal saline. Therefore, in the carotid artery, plaque components located on the far side of the luminal surface were sometimes not visualized by OCT due to its limited penetration depth. Recently, a new frequency domain OCT system was developed. This new system does not need occlusion of the target artery due to faster scanning (Table 3). Setacci et al. document the benefits of this new OCT system utilizing a non-occlusive technique in the carotid artery [13]. In their report, the new system not only safely eliminated the need to occlude the carotid artery, but also acquired good quality images and informative details before and after stenting. Notably, the new OCT catheter can visualize arteries up to 10 mm in diameter, encompassing the entire carotid artery. Thus, this new system seems to overcome the imitations of the previous iteration, allowing OCT to be applied safely, easily, and efficiently in the carotid artery. Future studies are expected to investigate the relationship between carotid plaques and

**Symptomatic Asymptomatic p-value**

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**(n=17) (n=17)**

for thrombus, ulceration, neovascularization, and lipid pool.

**Table 2.** OCT findings of symptomatic and asymptomatic lesions

**5. Limitations and recent advances of the OCT system**

stents with regard to stent design and plaque composition.

OCT findings

#### **4. Differences between symptomatic and asymptomatic plaques by OCT**

Another study to evaluate the ability of OCT to visualize carotid artery plaques as compared to that of IVUS in asymptomatic and symptomatic patients was performed 12. In this study, OCT was used for 34 plaques (17 symptomatic, 17 asymptomatic) in 30 patients during CAS under a proximal cerebral protection method. OCT was performed before balloon angioplasty and after stent placement. IVUS was performed after OCT. Among pre-stenting findings, intraluminal thrombus and neovascularization were significantly more frequently detected by OCT than by VH-IVUS (p<0.001). Ulceration also tended to be more frequently detected by OCT than by IVUS, but the difference was not significant (Table 1). Conversely, calcification was less frequently detected by OCT than by IVUS (p<0.001; Table 1). No difference in the detection of the lipid rich necrotic core was seen between OCT and IVUS (Table 1).

**Table 1.** Comparison of OCT and VH-IVUS findings

OCT detected differences between symptomatic and asymptomatic carotid plaques (Table 2): intraluminal thrombus was more frequently observed in symptomatic plaques (76.5%) than in asymptomatic plaques (11.8%; p<0.001); and, neovascularization was also more often observed in symptomatic plaques (58.8%) than in asymptomatic plaques (17.6%; p=0.03). In contrast, no significant differences were seen in the incidence of other findings such as calcification, lipid-rich necrotic core, ulceration, and plaque protrusion after stent placement between groups. *Interobserver* and intraobserver variability with OCT diagnosis was excellent for thrombus, ulceration, neovascularization, and lipid pool.

**Table 2.** OCT findings of symptomatic and asymptomatic lesions

during CAS, under a proximal cerebral protection method. In addition to intraluminal thrombus, fibrous cap disruption (Fig. 3) and plaque protrusion after stenting (Fig. 4) were easily detected by OCT. There were no technical or neurological complications in this series. OCT could best visualize the lateral side of lumen pathology (intraluminal thrombus or fibrous cap disruption) with a high resolution of 10 um, whereas IVUS, MRI, or computed tomography allowed assessment of the entire arterial wall, albeit with lesser resolution. OCT and IVUS thus complement each other and may aid in discriminating plaques that are eligible for CAS.

**4. Differences between symptomatic and asymptomatic plaques by OCT**

Another study to evaluate the ability of OCT to visualize carotid artery plaques as compared to that of IVUS in asymptomatic and symptomatic patients was performed 12. In this study, OCT was used for 34 plaques (17 symptomatic, 17 asymptomatic) in 30 patients during CAS under a proximal cerebral protection method. OCT was performed before balloon angioplasty and after stent placement. IVUS was performed after OCT. Among pre-stenting findings, intraluminal thrombus and neovascularization were significantly more frequently detected by OCT than by VH-IVUS (p<0.001). Ulceration also tended to be more frequently detected by OCT than by IVUS, but the difference was not significant (Table 1). Conversely, calcification was less frequently detected by OCT than by IVUS (p<0.001; Table 1). No difference in the

detection of the lipid rich necrotic core was seen between OCT and IVUS (Table 1).

Thrombus, n (%) 15 (44.1) 1 (2.9) <0.001 Neovascularization, n (%) 13 (38.2) 0 (0) <0.001 Ulceration, n (%) 3 (8.8) 0 (0) 0.24 Calcification, n (%) 13 (38.2) 34 (100)\* <0.001 Lipid, n (%) 28 (82.4) 30 (88.2)\*\* 0.73

Plaque protrusion, n (%) 6 (17.6) 0 (0) 0.032

OCT detected differences between symptomatic and asymptomatic carotid plaques (Table 2): intraluminal thrombus was more frequently observed in symptomatic plaques (76.5%) than in asymptomatic plaques (11.8%; p<0.001); and, neovascularization was also more often observed in symptomatic plaques (58.8%) than in asymptomatic plaques (17.6%; p=0.03). In contrast, no significant differences were seen in the incidence of other findings such as

\*: shown as 'dense calcified', \*\*: shown as 'fibrofatty and/or necrotic core' on VH-IVUS

Pre-stenting (n = 34)

122 Optical Coherence Tomography

Post-stenting (n = 34)

**Table 1.** Comparison of OCT and VH-IVUS findings

**OCT VH-IVUS p-value**

#### **5. Limitations and recent advances of the OCT system**

The major limitations of OCT are interference by blood flow and the degree of tissue penetra‐ tion. To obtain a bloodless field of view, a proximal protection method which uses occlusion balloons for the common and external carotid arteries is required for the application of OCT in the cervical carotid artery [8, 11, 12]. The scanning length of OCT was 3.25 to 3.4 mm in normal saline. Therefore, in the carotid artery, plaque components located on the far side of the luminal surface were sometimes not visualized by OCT due to its limited penetration depth. Recently, a new frequency domain OCT system was developed. This new system does not need occlusion of the target artery due to faster scanning (Table 3). Setacci et al. document the benefits of this new OCT system utilizing a non-occlusive technique in the carotid artery [13]. In their report, the new system not only safely eliminated the need to occlude the carotid artery, but also acquired good quality images and informative details before and after stenting. Notably, the new OCT catheter can visualize arteries up to 10 mm in diameter, encompassing the entire carotid artery. Thus, this new system seems to overcome the imitations of the previous iteration, allowing OCT to be applied safely, easily, and efficiently in the carotid artery. Future studies are expected to investigate the relationship between carotid plaques and stents with regard to stent design and plaque composition.

**References**

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111, 1551-5.

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[2] Hishikawa, T, Iihara, K, Ishibashi-ueda, H, et al. Virtual histology-intravascular ul‐ trasound in assessment of carotid plaques: ex vivo study. Neurosurgery (2009). , 65,

[3] Mintz, G. S, Nissen, S. E, Anderson, W. D, et al. American College of Cardiology clin‐ ical expert consensus document on standards for acquisition, measurement and re‐ porting of intravascular ultrasound studies (IVUS). A report of the American College of Cardiology task force on clinical expert consensus documents developed in collab‐ oration with the European society of cardiology endorsed by the society of cardiac

[4] Jang, I. K, Bouma, B. E, Kang, D. H, et al. Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravas‐

[5] Yabushita, H, Bouma, B. E, Houser, S. L, et al. Characterization of human atheroscle‐

[6] Jang, I. K, & Tearney, G. J. MacNeill B, et al. In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography. Circulation (2005). ,

[7] Kawasaki, M, Bouma, B. E, Bressner, J, et al. Diagnostic accuracy of optical coherence tomography and integrated backscatter intravascular ultrasound images for tissue characterization of human coronary plaques. J Am Coll Cardiol (2006). , 48, 81-8. [8] Yoshimura, S, Kawasaki, M, Yamada, K, et al. Demonstration of intraluminal throm‐ bus in the carotid artery by optical coherence tomography. Neurosurgery (2010).

[9] Kume, T, Akasaka, T, Kawamoto, T, et al. Assessment of coronary arterial thrombus

[10] Meng, L, Lv, B, Zhang, S, & Yv, B. In vivo optical coherence tomography of experi‐

[11] Yoshimura, S, Kawasaki, M, Yamada, K, et al. OCT of human carotid arterial pla‐

[12] Yoshimura, S, Kawasaki, M, Yamada, K, et al. Visualization of internal carotid artery atherosclerotic plaques in symptomatic and asymptomatic patients: a comparison of optical coherence tomography and intravascular ultrasound. AJNR Am J Neurora‐

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**Table 3.** Comparison of new and previous version of OCT

#### **6. Conclusions**