femoral head avascular necrosis ( fhavn ) is the result of irreversible anoxia of the subchondral bone .
fhavn is one of the increasing common causes of musculoskeletal disability that poses a major diagnostic and therapeutic challenge . with approximately 20,000 new reported cases each year , it is the underlying disease in as many as 10% of 500,000 total hip replacements annually performed in the usa . affecting mainly young men in their late 30s and early 40s , it results in manpower loss and adds to morbidity .
left untreated , fhavn will progress to secondary osteoarthritis in 80% of cases and eventually require total hip arthroplasty , hence the importance of early diagnosis is needed .
the causes of fhavn include trauma and nontraumatic causes such as long - term corticosteroid use , alcohol abuse , hematological diseases ( sickle cell anemia , thalassemia , polycythemia , hemophilia , and myeloproliferative disorder ) , metabolic diseases ( gaucher 's disease , hypercholesterolemia , pregnancy , chronic renal failure , hyperparathyroidism , and cushing 's disease ) , autoimmune diseases , chronic pancreatitis , caisson 's disease , radiation , congenital hip dislocation , and use of potent intravenous bisphosphonates .
various pathophysiologic mechanisms have been proposed to explain the occurrence of fhavn in these diverse conditions .
the proposed mechanisms of cell death include some form of arterial or venous insufficiency or extravascular compression in the context of a rigid bony compartment .
avascular necrosis ( avn ) is characterized by areas of dead trabecular bone and marrow that extend to involve the subchondral plate .
typically , the principal weight bearing region , the anterolateral aspect of the femoral head is involved , but any region of the femoral head may be involved . measures to preserve the joint
are associated with better prognoses when the diagnosis of fhavn is made early in the course of the disease .
the results of joint replacement therapy are poorer in younger age groups than in older patients .
it is , therefore , critical to diagnose this condition as early as possible to prevent or delay progression of the disease .
noninvasive diagnostic tests used in detecting avn include radiography , three - phase bone scintigraphy ( tpbs ) with or without single photon emission computed tomography / computed tomography ( spect / ct ) , conventional ct scan , and magnetic resonance imaging ( mri ) .
tc-99 m methylene diphosphonate ( mdp ) bone scintigraphy could be an ideal modality for assessing the reparative processes of osteonecrosis as the radionuclide activity reflects osteoblastic activity and blood flow . on planar scintigraphic images , the boundary of the necrotic lesion typically appears as a margin of increased tracer uptake adjacent to a photopenic area .
however , if the necrotic lesion is small or eccentrically located , it becomes difficult to detect the scintigraphic changes around the necrotic lesion .
thus , planar scintigraphic images suffer from important limitations such as poor spatial resolution and inability to quantify the lesion .
although spect , a technique involving three - dimensional scintigraphy , has been developed as a means of overcoming the limitations of planar scintigraphic images , the lack of anatomical detail makes it difficult to use often the information reliably .
uptake of f-18 fluoride , like that of tc-99 m mdp , depends on regional blood flow and osteoblastic activity .
however , positron emission tomography ( pet ) offers superior spatial resolution , and the favorable pharmacokinetic characteristics of f-18 fluoride make this a more sensitive modality than spect / ct . since pet / ct provides both structural and functional information , it has been proven useful for interpreting radionuclide uptake not only in patients with malignancies but also in nonmalignant conditions .
also , pet / ct provides an accurate evaluation of the site of the lesions with the ct part of the pet providing anatomical details .
however , to the best of our knowledge , there are no studies to date showing the utility of f-18 fluoride pet / ct bone scan in the diagnosis of fhavn .
the purpose of this study was to assess the utility of f-18 fluoride pet / ct bone scan in the diagnosis of fhavn and compare it with mri .
exclusion criteria included pregnancy , severe debilitation , contraindication to mri , and refusal to give written informed consent .
fifty - one consecutive patients ( 39 male , 12 female ) aged 1748 ( mean 32.5 ) years with high clinical suspicion of fhavn and referred for mri from a tertiary orthopedic care unit were prospectively evaluated .
all patients underwent mri and f-18 fluoride pet / ct bone scans within 410 ( mean 8) days of each other .
all patients underwent mri on a 3.0 t ( ge discovery mr750w ) mri unit with a body phased array coil .
the following sequences were used : t1  axial , sagittal , and coronal ( tr / te , 717/9.2 ) , t2 fs - axial and coronal ( tr / te , 4528/102 ) , pdfs - coronal ( tr / te , 275/30 ) , 1fs - coronal ( tr / te,576/9.2 ) .
one experienced radiologist ( ps ) and one experienced orthopedic surgeon ( rks ) read and staged the mri images .
diagnostic criteria for ficat staging pet / ct ( diagnostic ct ) of the pelvis ( including both hip joints ) was performed 1 h after intravenous injection of 370 mbq of f-18 fluoride on a dedicated pet / ct scanner ( discovery ste 16 ; ge healthcare , usa ) .
reconstruction of the acquired data was performed so as to obtain fused pet / ct images in transaxial , coronal , and sagittal views .
two patients with history of long - term steroid use for systemic lupus erythematosus ( sle ) , with pain in multiple joints underwent total body pet / ct .
two experienced nuclear medicine physicians ( ab , brm ) blinded to the mri reports read the pet / ct scans separately .
regions of interest ( rois ) were drawn separately over the photopenic area , and the entire head of the affected femur - and the maximum standardized uptake values ( suvmax ) of each of these were recorded . in patients with unilateral fhavn ,
all patients were followed up clinically for a mean period of 10 months ( range : 718 months ) .
a final diagnosis of fhavn was made by surgical pathology or clinical and radiologic follow - up .
spss ( statistical product and service solutions , version 16.0 , ibm , usa ) software was used for statistical analysis .
descriptive statistics such as mean and range were used to describe demographics and clinical profile of all patients .
sensitivity , specificity , and accuracy of mri and pet / ct compared to composite gold standard .
exclusion criteria included pregnancy , severe debilitation , contraindication to mri , and refusal to give written informed consent .
fifty - one consecutive patients ( 39 male , 12 female ) aged 1748 ( mean 32.5 ) years with high clinical suspicion of fhavn and referred for mri from a tertiary orthopedic care unit were prospectively evaluated .
all patients underwent mri and f-18 fluoride pet / ct bone scans within 410 ( mean 8) days of each other .
all patients underwent mri on a 3.0 t ( ge discovery mr750w ) mri unit with a body phased array coil .
the following sequences were used : t1  axial , sagittal , and coronal ( tr / te , 717/9.2 ) , t2 fs - axial and coronal ( tr / te , 4528/102 ) , pdfs - coronal ( tr / te , 275/30 ) , 1fs - coronal ( tr / te,576/9.2 ) .
one experienced radiologist ( ps ) and one experienced orthopedic surgeon ( rks ) read and staged the mri images .
diagnostic criteria for ficat staging pet / ct ( diagnostic ct ) of the pelvis ( including both hip joints ) was performed 1 h after intravenous injection of 370 mbq of f-18 fluoride on a dedicated pet / ct scanner ( discovery ste 16 ; ge healthcare , usa ) .
reconstruction of the acquired data was performed so as to obtain fused pet / ct images in transaxial , coronal , and sagittal views .
two patients with history of long - term steroid use for systemic lupus erythematosus ( sle ) , with pain in multiple joints underwent total body pet / ct .
two experienced nuclear medicine physicians ( ab , brm ) blinded to the mri reports read the pet / ct scans separately .
regions of interest ( rois ) were drawn separately over the photopenic area , and the entire head of the affected femur - and the maximum standardized uptake values ( suvmax ) of each of these were recorded . in patients with unilateral fhavn ,
all patients were followed up clinically for a mean period of 10 months ( range : 718 months ) .
a final diagnosis of fhavn was made by surgical pathology or clinical and radiologic follow - up .
spss ( statistical product and service solutions , version 16.0 , ibm , usa ) software was used for statistical analysis .
descriptive statistics such as mean and range were used to describe demographics and clinical profile of all patients .
sensitivity , specificity , and accuracy of mri and pet / ct compared to composite gold standard .
diagnostic criteria for fhavn on the pet / ct included a photopenic area surrounded by areas of reactive increased tracer uptake along with the  asterisk sign  ( loss of thickening of bone trabeculae in the center of the femoral head which appears similar to a star ) and  crescent sign  ( horizontal subchondral fracture ) on ct . findings on the ct part of the pet / ct like subchondral sclerosis
, subchondral cysts , loss of contour of the femoral head , and joint space narrowing were noted whenever present . presence of various diagnostic features on mri such as bone marrow edema , a circumscribed subchondral  band - like  lesion with low signal intensity on t1-weighted ( t1w ) sequences , double line sign ( an inner bright t2 line representing granulation tissue and an outer dark line representing sclerotic bone ) , rim sign ( a high t2 or intermediate t1 signal line sandwiched between two low signal lines ) , and joint effusion were noted when present .
thirty - nine of the 51 patients evaluated were diagnosed to have fhavn on mri ; 23 had unilateral , and 16 had bilateral femoral head involvement .
of the 55 hips diagnosed with avn , 7 were diagnosed to be ficat stage i , 19 stage ii , 25 stage iii , and 4 stage iv . using the criteria described earlier ,
fhavn was diagnosed on f-18 fluoride pet / ct in 57 hips including all 55 hips diagnosed on mri .
representative images of pet / ct and mri in a patient with bilateral fhavn are shown in figure 1 .
one patient diagnosed with bilateral early fhavn on pet / ct had imaging features indeterminate for avn on mri [ figure 2 ] . during 13 months of follow - up ,
this patient continued to have pain in both hips , and a subsequent mri showed ficat stage i fhavn on the right side and stage ii fhavn on the left side .
of the remaining 11 patients , 3 patients had degenerative arthritis , 4 had transient osteoporosis of the hip [ figure 3 ] , and 4 were normal on both imaging modalities
. a 24-year - old male patient with bilateral ficat stage iii femoral head avascular necrosis ( a ) coronal positron emission tomography , ( d ) axial positron emission tomography , ( f ) fused axial positron emission tomography / computed tomography images show photopenic areas ( arrows ) in the antero - superior regions of both femoral heads , corresponding to subchondral cysts surrounded by sclerosis on computed tomography ( b and e ) and decreased signal intensity on t2 weighted magnetic resonance ( c ) .
the photopenic areas are bordered by increased tracer uptake corresponding to bone marrow edema on magnetic resonance imaging .
note is also made of bilateral joint effusion , double - line sign in the right femoral head and rim sign in the left femoral head on magnetic resonance imaging ( c ) a 32-year - old female patient with bilateral hip pain for 6 months : ( a ) coronal positron emission tomography , ( d ) axial positron emission tomography , and ( e ) fused axial positron emission tomography / computed tomography images show photopenic areas ( arrows ) in the antero - superior regions of both femoral heads , with no definite morphological changes on computed tomography ( b and f ) and nonspecific marrow edema on mri ( c ) .
a diagnosis of bilateral early femoral head avascular necrosis was made on positron emission tomography / computed tomography while magnetic resonance imaging was indeterminate for avascular necrosis . during 13 months of follow - up , the patient continued to have pain in both hips and a subsequent magnetic resonance imaging showed ficat stage i femoral head avascular necrosis on the right side and stage ii femoral head avascular necrosis on the left side a 39-year - old male patient with left sided hip pain for 1-year : ( a ) coronal positron emission tomography , ( b ) fused coronal positron emission tomography / computed tomography , ( d ) axial fused positron emission tomography / computed tomography images show diffusely increased tracer uptake ( arrow ) in the head and neck of the left femur , ( e ) computed tomography showed no morphological changes ( c and f ) coronal and axial magnetic resonance imaging images show diffuse bone marrow edema extending up to the neck and decreased signal intensity from the 112 oclock position ( arrow ) in the left femoral head .
a diagnosis of transient osteoporosis of the hip was made which was proved on clinical follow - up by surgical pathology or clinical and radiologic follow - up , a final diagnosis of fhavn was made in 40 patients ( 57 hips ) .
final diagnosis in the rest was made by clinical or radiological follow - up , as they refused to undergo biopsy / surgical intervention .
seventeen ( 43% ) patients had a history of steroid use , 10 ( 24% ) of alcohol use , 7 ( 17% ) had trauma , 1 ( 2% ) was pregnancy - related and in 5 ( 14% ) no causative factor was identified .
mri was 96.5% sensitive , 100% specific , and 98.03% accurate in diagnosing fhavn , while pet / ct was 100% sensitive , specific and accurate in diagnosing fhavn .
the agreement between the two imaging modalities for the diagnosis of fhavn was 96.07% . using the rois drawn on the affected femoral head , the photopenic area and normal femoral head as described , mean ( range ) suvmax of the photopenic area was 1.9 ( 0.22.8 ) , affected femoral head was 21.3 ( 8.242.8 ) and normal femoral head was 4.4 ( 3.56.7 ) .
mean suvmax values for the affected femoral heads with ficat stage i , ii , iii , and iv were 10.9 , 23.1 , 27.8 , and 35.5 , respectively .
as the number of hips in different stages of avn varied , with only a few hips with stage i and iv disease , a cut - off value to stage avn based on suvmax alone could not be calculated .
however , it was observed that with increase in stage , suvmax value of the femoral head was also higher , representing increased ongoing reactive changes .
two patients with a history of long - term steroid use for sle and pain in multiple joints underwent total body pet / ct .
in addition to bilateral fhavn , one patient showed avn of both humeri and the other showed avn of the right distal end of the femur .
fhavn is a disease process for which progression is difficult to predict due to the varying etiology .
delayed intervention in undiagnosed fhavn leads to degenerative arthritis and eventual collapse of the femoral head , making early diagnosis crucial .
noninvasive diagnostic tests used in detecting avn include plain radiography , ct , mri , tpbs , and spect / ct .
on radiography , abnormal findings in avn include the  crescent sign  ( horizontal subchondral fracture line ) , cystic or sclerotic change in the femoral head , abnormal contours of the femoral head , and collapse or secondary degenerative change . however , the sensitivity of plain radiography for detecting early stages of the disease is as low as 41% .
demonstrated the sensitivity of tc-99 m mdp in demonstrating the absence of uptake in viable osteocytes by 72 h. they showed that initially a  cold  area is noted in the femoral head , indicating avascularity and reduced delivery of the radiopharmaceutical .
there may be a  doughnut  appearance , with a photopenic center surrounded by a region of hyperemia and reactive change .
subsequently , the photopenic area diminishes as there is ingrowth of osteoblasts upward from the metaphysis into the femoral head so that ultimately , as healing progress , there will be uniform intense radioactivity throughout . using a 1.5 t magnet , beltran et al . reported 88% sensitivity , 100% specificity , and 94% accuracy with mri and 78% sensitivity , 75% specificity , and 76% accuracy with bone scintigraphy .
spect scanning provides images of the radioactivity within the target organ in three dimensions . with this modality , overlying and underlying
areas of radioactivity may be separated into sequential tomographic planes , thus providing increased image contrast and improved lesion detection and localization , as compared with planar scintigraphy .
early in the disease , spect scans may demonstrate an avascular focus , which may be missed on mri unless contrast is used .
collier et al . found a sensitivity of 85% for spect scanning . with triple - head high - resolution
compared the diagnostic sensitivity of tc-99 m mdp bone spect and mri in the early detection of femoral head osteonecrosis after renal transplantation and showed a sensitivity of 100% ( 32/32 ) for spect and only 66% for mri .
evaluated a total of 22 patients and 24 symptomatic hips out of which seven hips ( 29% ) were confirmed to have avn and showed additional value of spect / ct versus spect in the diagnosis of fhavn .
they concluded that spect / ct conferred a benefit of improvement of area under curve in receiver operating characteristic in the diagnosis of hip avn compared with spect alone .
the reported sensitivity of mri for early diagnosis of osteonecrosis ranges between 88% and 100% . in the early stages of the disease , there may not be any alteration of the normal signal intensity of the femoral head .
the first sign of avn is nonspecific : diffuse areas of decreased signal intensity are seen in the normally high - signal - intensity fatty marrow on t1w images .
hence , there are chances that early avn may be missed in mri . while previous studies have demonstrated the utility of tpbs and spect in the diagnosis of avn , there are not many studies using spect / ct for detecting avn .
thus , the reported sensitivity and specificity of bone scintigraphy in the diagnosis of avn in the literature is either lower or comparable to mri . an earlier case report has described the use of f-18 fluoride pet / ct in the diagnosis of fhavn .
pet has better spatial resolution than spect ( 5 mm vs. ~1 cm respectively ) .
f-18 fluoride has favorable kinetics such as faster blood clearance and 2-fold higher uptake in bone compared to tc-99 m mdp .
it has higher capillary permeability and faster blood clearance , which results in better target to background ratio compared to mdp .
also , the high spatial resolution and contrast resolution of the ct component of pet / ct provides morphologic identification .
ct scanning is appropriate in evaluating the extent of involvement , such as subchondral lucencies and sclerosis during the reparative stage , before the onset of femoral head collapse and superimposed degenerative disease .
ct scanning also defines the extent of disease at stages ii and higher better than mri and plain film radiography . with multiplanar reconstruction
thus , hybrid pet / ct improves the sensitivity and specificity compared to pet alone .
however , f-18 fluoride pet / ct has slightly higher radiation dosimetry than tc-99 m mdp .
the estimated radiation dose in adult humans is 0.19 mgy / mbq compared to 0.03 mgy / mbq from tc-99 m mdp for the bladder wall and 0.0120 mgy / mbq compared to 0.035 mgy / mbq for the bone surfaces .
the final choice of mdp spect / ct or 18f - naf pet / ct would depend , to a large extent , on availability as well as costs involved .
the dynamics of naf allow for more rapid imaging ( within 1 h of tracer injection ) as compared to tc-99 m mdp allowing higher throughput in departments with high patient turnover .
imaging time with pet / ct is also much shorter compared to spect / ct .
as pet / ct provides better image resolution and allows for semi - quantitative analysis , f-18 fluoride pet / ct may be the preferred investigation in the diagnosis of fhavn .
while dynamic phase pet / ct may provide important information on femoral head vascularity , the increased scan duration may be perceived as a drawback .
the results of this study suggest that the 1-h static pet / ct image may be useful for a rapid evaluation of fhavn .
while the additional cost and radiation exposure of naf pet / ct ( compared to mdp spect / ct ) may limit the use of this investigation , the accurate diagnostic information obtained would tend to justify the use of this investigation , especially in postoperative patients with orthopedic hardware
. the cost will be significantly lower for institutes equipped with a medical cyclotron since no additional radiopharmaceutical preparation is required . in the present study ,
pet / ct has the advantage of detecting abnormalities at multiple sites without increasing the cost .
it can also be considered when a patient complains of pain at multiple bone and joint areas . in our study ,
quantitative bone scanning provides physiologic data that can not be obtained with other modalities , including mri and spect ; for example , this technique allows quantification of uptake , which can be used for prognostic purpose .
mri can not be performed in patients with cardiac pacemakers or when intracranial clips are present and is challenging in patients with claustrophobia .
it is difficult to detect fhavn after surgery using orthopedic hardware , which creates significant image distortion .
f-18 fluoride pet / ct can also be performed when results of mri are indeterminate .
the study group included patients with high suspicion of fhavn referred from a tertiary orthopedic care , which might have increased the sensitivity of the study .
also , histopathology , which is gold standard in the diagnosis of avn could not be obtained in all the cases , as it is invasive .
the study group included patients with high suspicion of fhavn referred from a tertiary orthopedic care , which might have increased the sensitivity of the study .
also , histopathology , which is gold standard in the diagnosis of avn could not be obtained in all the cases , as it is invasive .
f-18 fluoride pet / ct showed good agreement with mri in the initial diagnosis of fhavn . it can be especially useful in detecting early disease and also in patients in whom mri is contraindicated .
 objective : femoral head avascular necrosis ( fhavn ) is one of the increasingly common causes of musculoskeletal disability and poses a major diagnostic and therapeutic challenge . 
 although radiography , scintigraphy , computed tomography ( ct ) , and magnetic resonance imaging ( mri ) have been widely used in the diagnosis of fhavn , positron emission tomography ( pet ) has recently been evaluated to assess vascularity of the femoral head . in this study , the authors compared f-18 fluoride pet / ct with mri in the initial diagnosis of fhavn.patients and methods : we prospectively studied 51 consecutive patients with a high clinical suspicion of fhavn . all patients underwent mri and f-18 fluoride pet / ct , the time interval between the two scans being 410 ( mean 8) days . 
 two nuclear medicine physicians blinded to the mri report read the pet / ct scans . 
 clinical assessment was also done . 
 final diagnoses were made by surgical pathology or clinical and radiologic follow-up.results:a final diagnosis of avascular necrosis ( avn ) was made in 40 patients . 
 mri was 96.5% sensitive , 100% specific , and 98.03% accurate while pet / ct was 100% sensitive , specific , and accurate in diagnosing fhavn . 
 the agreement between the two imaging modalities for the diagnosis of avn was 96.07%.conclusion : f-18 fluoride pet / ct showed good agreement with mri in the initial diagnosis of fhavn and can be better than mri in detecting early disease . 