**2.2. Principles of laser thermal therapy**

under stereotactic guidance, and the size of the lesion produced as a result of laser ablation is monitored using MR thermography in real time. The minimal invasiveness of the procedure makes it a good choice in patients that cannot tolerate a large operation due to either burden

Glioblastoma is a diffuse primary brain neoplasm with poor prognosis. The invasive nature and malignant potential of this tumor make its treatment a challenge. The current standard of care management paradigm consists of a multidisciplinary approach by combining maximal safe tumor resection with subsequent chemotherapy and radiation [1]. Despite maximal treatment, survival rates of glioblastoma remain poor with median survival of 14–16 months. Recent evidence indicates, however, that the extent of resection of high-grade gliomas correlates with patient survival [2–6]. In a similar sense, laser ablation can provide effective tumor cytoreduction to maximize the effectiveness of adjuvant treatments. Furthermore, there is promising evidence that hyperthermia may have additional synergistic effects with radiation, as well as disrupt blood-brain barrier (BBB) and thus facilitate chemotherapy delivery to target tissues [7, 8].

The following chapter will focus on describing the principles of laser ablation and the equipment used to deliver laser energy to brain tumors, as well as discussing current evidence for

The concept of using heat to destroy cancerous tissue has been attempted multiple times in the past. It was, however, difficult to develop a mechanism of heat delivery to the affected tissues that would allow controlled ablation of tissues in question. One of the earliest references to the efficacy of mild hyperthermia in cancer destruction is found in 1891 in the report by Dr. Coley, an orthopedic surgeon, who made an observation of complete resolution of an inoperable sarcoma in a patient after *Streptococcus pyogenes* infection [9]. He suggested that the high fevers that accompany the illness injured cancer cells sufficiently to destroy them. He followed up that work by describing a series of 10 patients that were successfully treated with "bacterial toxin therapy" [9]. Unfortunately, his results were not reproduced by others. In the years to come, radiation therapy and chemotherapy have established themselves as mainstream treatments for cancer. It was not until 1967 when Cavaliere et al. demonstrated selective sensitivity to heat of cancer cells, thus suggesting the use of hyperthermia as part of cancer therapy [10]. Follow-up work in animal models corroborated that notion. It was demonstrated that hyperthermia preferentially affects glioma cells compared to surrounding brain tissue. Local hypoxia and more acidic microenvironment within tumor contributes to this selective sensitivity to heat of glioblastoma [11]. Furthermore, hyperthermia potentiates

Other factors, however, influence the effectiveness of hyperthermia. In vitro experiments showed that only 50% of sarcomas were responsive to hyperthermia resulting in tumor

the use of laser thermal therapy in management of high-grade gliomas.

the effects of radiation and chemotherapy observed in vitro [12–14].

of disease or poor performance status.

188 Glioma - Contemporary Diagnostic and Therapeutic Approaches

**2. Background**

**2.1. The use of hyperthermia**

Laser interstitial therapy is an ablative technique that results in tissue destruction as a result of heating. Photons produced by the laser light are absorbed by the surrounding tissues causing excitation and release of excess energy as heat [18]. Once the critical thermal threshold is reached, protein denaturation and irreversible tissue coagulation ensues resulting in permanent tissue damage.

The first lasers that were attempted for tissue ablation were ruby-based [19]. The amount of energy and thus tissue damage produced by these lasers was difficult to control. In 1983, Bown et al. first described the use of the neodymium-doped yttrium aluminum garnet (Nd:YAG) laser for tissue ablation [20]. At present, two commercially available FDA-approved systems are available for use in neurosurgery in the United States: The NeuroBlate System (Monteris Medical, Plymouth, MN) and the Visualase Thermal Therapy System (Medtronic Inc., Minneapolis, MN). Laser ablation uses laser energy in the near-infrared range where the main tissue interactions are heating and coagulation (as opposed to cutting for the CO2 laser). Both commercial laser ablation systems use diode lasers—one at the Nd:YAG wavelength (1064 nm) and the other at 980 nm. Although there have been claims that one is superior to the other, these are not founded in fact [21]. Lasers in this near-infrared range only penetrate a few millimeters into brain tissue. This heat is then propagated by conduction to allow for ablation radii that may extend up to 15–20 mm.

The wavelength of the laser light is what determines the efficiency of energy transfer to the tissues and, as a result, the volume of the lesion produced. Furthermore, the duration of tissue exposure to the laser light affects the amount of energy transferred and thus the amount of heating produced, with longer duration of exposure resulting in higher temperatures achieved in exposed tissues [22–24]. The design of the optical fiber and the laser catheter further affects the properties of the laser. Initially, lasers had to be used at very low power (1–5 W) to avoid excessive heating that results in tissue charring. Improvement in laser catheter design with the development of cooling mechanisms allowed use of higher power while still protecting nearby tissues. This also provides a non-stick catheter surface that allows the laser probe to glide easily through tissues. Current cooling systems employed in laser probe design use either cooled gas system with CO2 , or a continuous flow of saline through a sheath surrounding the optic fiber.

The laser probe tip is made of either sapphire or quartz to avoid altering the optical properties of the laser light. This design results in a spherical light distribution at the tip of the probe, and as a result, thermal energy is delivered in a symmetrical ellipsoid shape that is centered along the probe axis. The NeuroBlate System, in addition to the spherical probe design, also offers a side-firing probe which allows the surgeon to robotically control the direction of maximal heat distribution and may have an advantage in treating irregularly shaped lesions, or lesions near eloquent areas.

frequency, and this difference is used to interpolate local temperature using well defined relationship [18, 33]. MR thermography does not measure the actual temperature of tissue, rather the change in temperature over time, therefore an accurate core temperature is required at the start of each ablation. The Arrhenius model is then applied to estimate the degree of tissue damage that is produced based on the temperature and the amount of time that the tissues are exposed to a given temperature. Subsequently, computer software is used to visualize the temperature damage produced in real time with accurate temporal and special resolution.

Laser Interstitial Thermal Therapy in Glioblastoma http://dx.doi.org/10.5772/intechopen.77078 191

Heating tissue results in different types of tissue damage. Several different zones of tissue damage have been described. Heating tissues to up to 40°C typically does not disrupt cellular homeostasis. Once the temperature increases in the range of 42–45°C, the cells display marked susceptibility to cellular damage [34]. This range is typically explored in hyperthermia experiments. Further increase in temperature from 46 to 60°C results in significant cytotoxicity and consequent rapid cell death [35]. At temperatures exceeding 60°C, the damage sustained by mitochondrial enzymes, as well as cellular nucleic acids and proteins is so severe that coagulative necrosis takes place [36]. Finally, heating tissues to near boiling temperatures results in charring, tissue evaporation and carbonization, that may result in life-threatening intracranial pressure increases if not immediately relieved. In addition to temperature thresholds, the length of time that the tissue exposed to a particular temperature determines the extent of tissue damage with longer exposures resulting in equivalent damage that is observed at higher temperatures [18]. For instance, heating tissues to 43°C for 2 min will result in reversible tissue damage. Whereas heating tissues to this temperature for 10 min will result in permanent

As tissue heating occurs, concentric zones of damage can be identified [18, 37–39]. In the area around the fiber, the temperatures can reach high numbers in excess of 60°C resulting in central core area of coagulative necrosis. If the temperature in the area adjacent to the fiber inadvertently reaches 100°C, tissue vaporization occurs and a pseudocavity is formed. Immediately outside the core area lies the intermediate zone of permanently damaged tissue with increased interstitial fluid content. The outermost zone of damage that represents marginal zone consists of edematous but viable brain tissue. Histologically, the marginal zone is defined by lack of evidence of apoptosis and vessel thrombosis, and containing axonal swelling, shrinking neurons, and hypertrophied endothelial cells—markers of reversible tissue injury. Following a laser ablation procedure, tissues typically exhibit an increase in size due to the presence of necrotic tissue and perilesional edema. Over time, however, the necrotic core of the lesion is replaced by granulation tissue resulting in lesion shrinkage and scar formation.

The typical appearance of high grade glioma is an irregular and heterogeneously enhancing lesion on T1-weighted images. After treatment, there are typical changes that are observed on subsequent imaging studies [40–42]. Immediately after procedure one can appreciate an area of hyperintensity within the lesion on T1-weighted MRI images. This finding corresponds to

**2.4. Biological effect of LITT**

**2.5. Radiographic appearance**

injury, and for 60 min will result in coagulative necrosis.

The Visualase system uses a 15 W 980 nm diode laser that is cooled with circulating sterile saline solution [25]. The diameter of the catheter is 1.65 mm. The laser probe tip comes with a light diffusing tip that results in spherical light distribution producing an ellipsoid area of tissue damage. This non-pulsed system produces faster lesions but the application of heat is limited to several minutes. The system is connected to a workstation that displays real-time thermography data as "thermal" and "damage" images [26, 27]. A number of safe points can be set on the pre-treatment MRI, and when the set temperature is reached at that point, the laser is deactivated.

The NeuroBlate System uses a 12 W solid-state Dornier diode laser that operates at Nd:YAG wavelength of 1064 nm [28]. The laser catheter is cooled with CO2 gas [29]. The probes come in two diameters: 3.2 and 2.2 mm. The light diffusing tip comes in two configurations: spherical, used to produce elliptical lesions along the probe axis, and side-firing probes, that enable treatment of complex and irregularly shaped lesions. The computer interface displays thermal damage as thermal-damage-threshold (TDT) lines. The yellow line represents tissue volume that is exposed to the equivalent of 43°C for 2 min, the blue line is equivalent to exposure to 43°C for 10 min, and the white line surround the volume that received the equivalent of thermal energy of 43°C for 60 min. Based on the Arrhenius equation, the higher the temperature, the less time it takes to generate each TDT-line.

### **2.3. MR thermography**

The use of laser ablation for treatment of tumors was first described by Bown in 1983 [20]. The first report of intracranial use for brain lesion laser ablation came out in 1990 [22]. Despite that, laser interstitial thermal therapy did not gain wide-spread use due to lack of the ability to monitor the extent of ablation and tissue damage. A variety of methods were attempted to measure thermal energy delivered to tissues and included skin thermometers, subcutaneous and interstitial probes, infrared detectors, and thermographic cameras, none of which were accurate enough to predict the size of the resulting thermal lesion [30–32]. Introduction of MR thermography revolutionized the application of laser thermal therapy since for the first time it allowed monitoring of the extent of tissue damage in real time [27]. The principle of MR thermography relies on detecting differential temperature-specific proton resonance frequency in the water molecules. At a given temperature, a proportion of water molecules are interconnected in space via hydrogen bonds between molecules. As the temperature of tissues increase during laser ablation, more water molecules are freed up from the hydrogen bonds between H2 O molecules. During application of the magnetic field, proton nuclei within free water molecules are mobilized more effectively resulting in a different proton resonance frequency, and this difference is used to interpolate local temperature using well defined relationship [18, 33]. MR thermography does not measure the actual temperature of tissue, rather the change in temperature over time, therefore an accurate core temperature is required at the start of each ablation. The Arrhenius model is then applied to estimate the degree of tissue damage that is produced based on the temperature and the amount of time that the tissues are exposed to a given temperature. Subsequently, computer software is used to visualize the temperature damage produced in real time with accurate temporal and special resolution.


**II. Implement** [43–46]

*Verb.* /ˈɪmplɪmɛnt/

Dates from the early 18th century.

Meaning: 1. To put (a decision, plan, agreement, etc.) into effect.

From Late Latin*: implementum*; *implere*: filling up.

Made of two Latin vocables

1. In (towards the center)

2.Plere (to fill up) (Greek polis, many)


Temporomandibular Joint Pain

*KadarkaraiKirupa, R. Rajashri, Kamali Raman, Aishwarya Balaji, Pavithra Elango, Swetha Karupaiah and Leelavathy Gopalakrishnan*

## **Abstract**

Temporomandibular joint (TMJ) is a synovial articulation between mandibular condyle and glenoid fossa in the temporal bone. Any structural and/or functional changes can affect the TMJ and related structures. Temporomandibular disorder (TMD) is a heterogeneous group of musculoskeletal disorders mainly characterised by regional pain in the facial and preauricular area and/or limitations/interference of jaw movement. TMD has multifactorial aetiology, which includes biology, and environmental social, emotional, and cognitive factors. TMD is more common orofacial pain condition and nondental origin. Factors associated with TMD include other pain condition, auto-immune disorder and psychiatric illness. The clinical conditions may present with limitation in opening and closing mouth, pain and articular noise. So this chapter mainly deals with the classification of TMJ disorder, diagnosis and management particularly TENS and ultrasound therapy for TMJ disorder.

**Keywords:** temporomandibular joint, TMJ disorders, TENS, pain, ultrasound therapy

## **1. Introduction**

The temporomandibular joint (TMJ) is a synovial joint. The joint is the articulation between the mandibular condyle and the glenoid fossa in the temporal bone. Temporomandibular joint disorders produce structural and functional changes of the joint. Temporalis, medial & lateral pterygoid, Masseter Maxilla/upper jaw Mandible/ lower jaw and the temporal. These disorders may present with specific clinical features such as pain, muscle tightness, limitation in opening and closing the mouth [1].

TMJ is the most complex joint. TMJ disorders occur when the muscles, ligament, joint capsule or any other structure surrounding the TMJ joint are affected. This consists of joint cavity, mandibular condyle, articular disc, muscle and nerve, which interacts with various structures such as cervical spine and orofacial region. When the physiological functions of some of these components are altered, functional and structural disorders result in clinical impact [2]. The unique feature of TMJ is that it acts as a fulcrum in which the movement is controlled by both morphology of joints and the dentition at the other end.

During life, the components of the joints including temporal, condylar and disc articular surfaces undergo continuous remodelling. The synovial fluid is responsible for nourishment and lubrication. The lateral pterygoid muscle is attached to the joint capsule. The function of the articular disc is to produce friction, stabilisation and viscoelastic properties. Mastication and speech are the main action of TMJ joint [3].

During mastication process, this joint supports a large number of forces. Excessive force on the joint can cause damage in its structure or alter normal function contact of condyles, discs and eminence. This damage and alteration can result in pain, dysfunction or both [3].

Temporomandibular disorders (TMDs) are group of heterogeneous musculoskeletal disorders mainly responsible for regional pain in the facial and preauricular, limitation and interference of the jaw movements. TMD has many causes, which includes biologic, environmental, social, emotional and cognitive factors. Factors associated with TMD include other pain condition (e.g. chronic headaches, fibromyalgia), autoimmune disorders, sleep apnoea and psychiatric illness. TMDs are the most common orofacial pain conditions other than dental origin [4].

Numerous risk factors have been implicated including joint and muscle trauma, anatomical factors (e.g. skeletal and occlusal relationship), pathophysiological factors (e.g. bone and connective tissue disorders, sensitization of peripheral and CNS pain processing pathways) and psychosocial factors (e.g. depression and anxiety, emotional and perceptual responses to psychological stressors).

### **2. Prevalences**

The prevalence of TMDs is around 12% of world population and 35 million people in US. TMDs affect both men and women but majority seeking care are women of age group 19–49 years. TMD is diagnosed in women 2–5 times more frequently than men. Studies suggest that women tend to have more severe symptoms and are nine times as likely to be diagnosed with majority limitations in jaw movements and unremitting pain.

There are various hypothesis put forward by several researchers to demonstrate the higher prevalence rate in women. Anatomical, hormonal, behavioural and genetic differences contribute to the disproportional ratio of women to men diagnosed [4].

**Anatomical differences** between males and females in jaw and skull affect the forces on TMJ. Maxillary bone is longer, wider and thicker in males than in females. The angle created by mandible is less obtuse in male than in female. Mandibular condyle is larger and temporal socket is deeper in males. All these anatomical factors create more stable environment for TMJ translation in males than in females.

**Hormonal differences** between men and women contribute to TMDs. Oestrogen and progesterone levels are higher in women during childbearing years. There is increased ligament laxity during preovulatory phase (oestrogen dominates). During follicular phase (days 1–9), relaxin hormone is secreted and it peaks during the luteal phase (days 15–28). These differences in the level of hormones released may contribute to greater laxity in some women. Increased ligament laxity increases joint play and it irritates the joints.

**Behavioural differences**—Men and women manage stress differently. Clenching, grinding and poor breathing habits can increase internalisation of stress and it may irritate TMJ [5].

Various studies revealed that at least one sign of articular dysfunction is seen in about 40–75% of cases in general adult population, and in 33% of cases, there is at least one symptom of dysfunction. Signs such as noise and asymmetric mouth

*Temporomandibular Joint Pain DOI: http://dx.doi.org/10.5772/intechopen.104842*

opening are prevalent in about 50% of the individuals and other symptoms such as difficulty in mouth opening are present in about 5% of cases [6]. Articular disorders are present in 19%, muscular forms of disorders in 23% and both in 27% of individuals in general population. In patients, these symptoms are more pronounced in 20–40 age group, and in general population, these symptoms are most commonly seen in 17–30 age groups.

Prevalence of moderate or severe TMDs was found to be 37.4% in children and adolescents between 6 and 14 years of age in Brazilian study.

Epidemiological surveys reported that 50–70% of population have signs of a disorder at some stage during their life, whereas an estimated 20–25% of the population have symptoms of TMD. The highest prevalence of TMD in relation to age has been estimated between the age of 20 and 40s. Among the post-menopausal women, those receiving hormone replacement therapy (HRT) were found to be at higher risk for TMD than those not receiving HRT. TMD is most prevalent in adolescents and women during the reproductive years and falls off sharply with advancing middle age [7].