Clinical impact of dual-tracer FDOPA and FDG PET/CT for the evaluation of patients with parkinsonian syndromes.

Parkinsonian syndromes include typical cases of idiopathic Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) associated with cognitive and vegetative disorders, which are more challenging to diagnose. The aim of this study was to assess -the value of dual-tracer imaging 6-fluoro-(18F)-L-DOPA (FDOPA) and fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), performed in routine patients demonstrating extrapyramidal signs and cognitive complains, for the diagnosis and management of parkinsonian syndromes.We retrospectively included 143 consecutive patients who underwent both FDOPA PET/CT (for the evaluation of parkinsonism) and FDG PET/CT (for the evaluation of cognitive complaints) in the same institution. The suspected clinical diagnosis before imaging and the final post-imaging diagnosis were collected by a dedicated questionnaire.FDOPA was pathological in 90.2% of cases, including 74.1% of PD, 3.5% of parkinsonian dementia and 7% of APS. FDG was normal or near normal in 58.7% of patients. A pattern of diffuse cortical hypometabolism was observed in the remaining patients, more frequently in APS than in PD patients (P = .001). Importantly, in 7.7% of cases dual-tracer PET/CT allowed to decide between several diagnostic hypotheses and led to a new diagnosis in 14.0%. Therefore, the management of these patients was modified, with clinical re-evaluation in a specialized unit and a control of neuropsychological tests and imaging.Dual-tracer PET/CT imaging may be a precious help in the diagnosis and management of parkinsonian syndromes.

Brain 18F-FDG PET Metabolic Abnormalities in Patients with Long-Lasting Macrophagic Myofascitis.

The aim of this study was to characterize brain metabolic abnormalities in patients with macrophagic myofascitis (MMF) and the relationship with cognitive dysfunction through the use of PET with 18F-FDG. Methods:18F-FDG PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (age [mean ± SD], 45.9 ± 12 y; 74% women). Images were analyzed with statistical parametric mapping (SPM12). Through the use of analysis of covariance, all 18F-FDG PET brain images of MMF patients were compared with those of a reference population of 44 healthy subjects similar in age (45.4 ± 16 y; P = 0.87) and sex (73% women; P = 0.88). The neuropsychological assessment identified 4 categories of patients: those with no significant cognitive impairment (n = 42), those with frontal subcortical (FSC) dysfunction (n = 29), those with Papez circuit dysfunction (n = 22), and those with callosal disconnection (n = 7). Results: In comparison with healthy subjects, the whole population of patients with MMF exhibited a spatial pattern of cerebral glucose hypometabolism (P < 0.001) involving the occipital lobes, temporal lobes, limbic system, cerebellum, and frontoparietal cortices, as shown by analysis of covariance. The subgroup of patients with FSC dysfunction exhibited a larger extent of involved areas (35,223 voxels vs. 13,680 voxels in the subgroup with Papez circuit dysfunction and 5,453 voxels in patients without cognitive impairment). Nonsignificant results were obtained for the last subgroup because of its small population size. Conclusion: Our study identified a peculiar spatial pattern of cerebral glucose hypometabolism that was most marked in MMF patients with FSC dysfunction. Further studies are needed to determine whether this pattern could represent a diagnostic biomarker of MMF in patients with chronic fatigue syndrome and cognitive dysfunction.

Brain (18)F-FDG, (18)F-Florbetaben PET/CT, (123)I-FP-CIT SPECT and Cardiac (123)I-MIBG Imaging for Diagnosis of a "Cerebral Type" of Lewy Body Disease.

A 67-year-old man was referred for fluctuating neuropsychiatric symptoms, featuring depression, delirious episodes, recurrent visual hallucinations and catatonic syndrome associated with cognitive decline. No parkinsonism was found clinically even under neuroleptic treatment. (18)F-FDG PET/CT showed hypometabolism in the posterior associative cortex including the occipital cortex, suggesting Lewy body dementia, but (123)I-FP-CIT SPECT was normal and cardiac (123)I-MIBG imaging showed no signs of sympathetic denervation. Alzheimer's disease was excluded by a normal (18)F-florbetaben PET/CT. This report suggests a rare case of α-synucleinopathy without brainstem involvement, referred to as "cerebral type" of Lewy body disease.

Functional imaging of hepatocellular carcinoma using diffusion-weighted MRI and (18)F-FDG PET/CT in patients on waiting-list for liver transplantation.

BACKGROUND: To compare the apparent diffusion coefficient (ADC) on diffusion-weighted imaging (DWI) with the standardized uptake values (SUV) measured by(18)F-FDG-PET/CT in naïve hepatocellular carcinoma (HCC) nodules, and to determine whether these markers are associated with tumours at high-risk of aggressiveness. METHODS: From 2007 to 2010, all patients with HCC on the waiting list for liver transplantation and who underwent both FDG-PET/CT and 1.5-T DWI-MRI (b values: 0, 200, 400, and 800 s/mm(2)) were included in this institutional review board-approved retrospective study. Tumour size, tumour ADC, tumour-to-liver ADC ratio (ADCT/L), maximal tumour SUV and tumour-to-liver SUV ratio (SUVT/L) were measured and compared to serum alpha-fetoprotein (AFP) levels, tumour size and differentiation grade on explanted specimens. RESULTS: A total of 37 HCC nodules in 28 patients were available for correlation between MRI and PET/CT, 7 of which (in 7 patients) showed a SUVT/L > 1.15. We did not find any correlation between tumour ADC or ADCT/L and tumour SUV or SUVT/L. To note, SUVT/L was positively correlated with AFP levels (R = 0.95, P ≤ 0.0001), while ADCT/L was not (P = 0.73). Twenty-four patients (with 32 nodules) underwent liver transplantation. In this subgroup, an increased SUVT/L ratio was associated with larger tumours (average size, 32 ± 14 mm; range, 18-60 mm; P < 0.0001) and with poor differentiation on pathology (grades 3 and 4; P = 0.04), while ADCT/L was neither associated with tumour size or differentiation grade. CONCLUSIONS: ADC and SUV measures in HCC nodules are not correlated. SUVT/L ratio correlates with AFP levels, tumour size and poor differentiation, and should probably be integrated as a co-variable in a predictive outcome model of patients on the waiting-list for liver transplantation.

[18F]-NaF PET/CT imaging in cardiac amyloidosis.

Cardiac amyloidosis (CA) is recognized as a common cause of restrictive cardiomyopathy and heart failure due to the deposition of insoluble proteins in the myocardial interstitium. We emphasize the role of [18F]-sodium fluoride (NaF) PET/CT as a potential noninvasive tool to identify and differentiate the transthyretin-related cardiac amyloidosis from the light-chain cardiac amyloidosis. We report cases of a 73-year-old man and a 75-year-old woman followed in our center for congestive heart failure with marked alteration of the left ventricular ejection fraction due to familial transthyretin Val122Ile cardiac amyloidosis and light-chain cardiac amyloidosis, respectively, confirmed on endomyocardial biopsy.

Neuropsychological Correlates of Brain Perfusion SPECT in Patients with Macrophagic Myofasciitis.

BACKGROUND: Patients with aluminum hydroxide adjuvant-induced macrophagic myofasciitis (MMF) complain of arthromyalgias, chronic fatigue and cognitive deficits. This study aimed to characterize brain perfusion in these patients. METHODS: Brain perfusion SPECT was performed in 76 consecutive patients (aged 49±10 y) followed in the Garches-Necker-Mondor-Hendaye reference center for rare neuromuscular diseases. Images were acquired 30 min after intravenous injection of 925 MBq 99mTc-ethylcysteinate dimer (ECD) at rest. All patients also underwent a comprehensive battery of neuropsychological tests, within 1.3±5.5 mo from SPECT. Statistical parametric maps (SPM12) were obtained for each test using linear regressions between each performance score and brain perfusion, with adjustment for age, sex, socio-cultural level and time delay between brain SPECT and neuropsychological testing. RESULTS: SPM analysis revealed positive correlation between neuropsychological scores (mostly exploring executive functions) and brain perfusion in the posterior associative cortex, including cuneus/precuneus/occipital lingual areas, the periventricular white matter/corpus callosum, and the cerebellum, while negative correlation was found with amygdalo-hippocampal/entorhinal complexes. A positive correlation was also observed between brain perfusion and the posterior associative cortex when the time elapsed since last vaccine injection was investigated. CONCLUSIONS: Brain perfusion SPECT showed a pattern of cortical and subcortical changes in accordance with the MMF-associated cognitive disorder previously described. These results provide a neurobiological substrate for brain dysfunction in aluminum hydroxide adjuvant-induced MMF patients.

Clinical routine use of dopamine transporter imaging in 516 consecutive patients.

[(123)I]-FP-CIT is a single photon emission computed tomography (SPECT) ligand showing in vivo the loss of dopaminergic terminals in the brain and is now available in the market. Despite several systematic studies in clinically inconclusive cases, the use of such imaging in clinical routine is scarcely reported. We analyzed 516 files of subjects with movement disorders who were consecutively examined using [(123)I]-FP-CIT scan and determined whether the use of imaging was appropriate and if it improved clinical diagnosis or care of the patient. In addition, we determined if appropriate use was related to subspecialties in Neurology, e.g., movement disorders' specialists vs. general neurologists, and if appropriate use was increasing over time. Among the 516 scans, 18% were in agreement with the license, 62% were classified as appropriate and 37% were considered inappropriate. A change of management was obvious in 60% of patients, but in 92% of those with an appropriate request vs. 13% of patients with an inappropriate request. Movement disorders' specialists had more appropriate requests than other practitioners. Eventually, comparing the first 100 vs. the last 100 quantified SPECT, performed more than 2.5 years apart, we found no difference for the appropriateness of the examination. The use of [(123)I]-FP-CIT imaging in clinical routine does not fit a restrictive license. An inappropriate use is seen in nearly 40% of cases, which reduces the real cost-effectiveness of the technique suggesting a need for continuing medical education on the topic.

Clinical impact of contrast-enhanced computed tomography combined with low-dose (18)F-fluorodeoxyglucose positron emission tomography/computed tomography on routine lymphoma patient management.

This study evaluated the clinical impact of contrast-enhanced computed tomography (CECT) on routine management of patients with lymphoma. Over a 1-year period, 237 CECT scans were performed prospectively in 163 patients after low-dose (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT). Scans were performed at staging (n = 41), interim (n = 73), post-therapy (n = 115) and follow-up (n = 8). Clinical impact was determined from the multidisciplinary committee reports. CECT had no clinical impact in 219 cases (92%). A clear impact was noted in only 3%, i.e. up-staging of lymphoma (n = 2) and diagnosis of deep vein thrombosis (n = 5). A debatable impact was noted in the remaining 11 cases, consisting of additional investigations, either without therapeutic impact (n = 8), or resulting in delay of therapy onset (n = 2) or ablative surgery (n = 1). CECT delivered an average 33.5 ± 3.8 mSv vs. 17.7 ± 2.8 mSv for PET/CT. In conclusion, the clinical impact of CECT seems limited, although scarce, life-threatening conditions were diagnosed. Imaging of lymphoma needs optimization to reduce radiation exposure.

Improvement of early 18F-FDG PET interpretation in diffuse large B-cell lymphoma: importance of the reference background.

UNLABELLED: This study investigated whether the reference background above which a residual mass is considered positive in the International Harmonization Project criteria should be modified for early (18)F-FDG PET evaluation. METHODS: In 92 patients with newly diagnosed diffuse large B-cell lymphoma, the maximal standardized uptake value (SUVmax) was measured on post-cycle 2 PET in the most intense residual mass (or, in the case of negative PET findings, in the area of most intense tumor uptake before therapy), in the mediastinal blood pool (MBP) and the liver, as potential reference background tissues. RESULTS: With MBP as a reference (SUVmax, 2.0 ± 0.6), PET was unable to distinguish early responders from nonresponders. In contrast, with liver as a reference (SUVmax, 2.5 ± 0.7), 2-y progression-free survival was significantly different between patients with PET-negative findings (81.8% [95% confidence interval, 71%-93%]) and patients with PET-positive findings (51.8% [95% confidence interval, 35%-69%], P = 0.003). CONCLUSION: When assessing early response, particularly in risk-adapted therapeutic trials, it seems preferable to refer to a background tissue (liver) with a higher level of uptake than that of current international criteria (MBP) which were designed for end-of-treatment evaluation.

Whole-body diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient mapping for staging patients with diffuse large B-cell lymphoma.

OBJECTIVE: To design a whole-body MR protocol using exclusively diffusion-weighted imaging (DWI) with respiratory gating and to assess its value for lesion detection and staging in patients with diffuse large B-cell lymphoma (DLBCL), with integrated FDG PET/CT as the reference standard. METHODS: Fifteen patients underwent both whole-body DWI (b = 50, 400, 800 s/mm(2)) and PET/CT for pretreatment staging. Lymph node and organ involvement were evaluated by qualitative and quantitative image analysis, including measurement of the mean apparent diffusion coefficient (ADC). RESULTS: A total of 296 lymph node regions in the 15 patients were analysed. Based on International Working Group size criteria alone, DWI findings matched PET/CT findings in 277 regions (94%) (kappa score = 0.85, P < 0.0001), yielding sensitivity and specificity for DWI lymph node involvement detection of 90% and 94%. Combining visual ADC analysis with size measurement increased DWI specificity to 100% with 81% sensitivity. For organ involvement, the two techniques agreed in all 20 recorded organs (100%). All involved organ lesions showed restricted diffusion. Ann Arbor stages agreed in 14 (93%) of the 15 patients. CONCLUSION: Whole-body DWI with ADC analysis can potentially be used for lesion detection and staging in patients with DLBCL.

Sentinel node localization should be interpreted with caution in midline vulvar cancer.

OBJECTIVE: Carcinomas of the vulva situated on the midline or close to it, are supposed to have a bilateral lymphatic drainage. The aim of this study was to evaluate sentinel node identification in these tumors. METHODS: Between April 2002 and February 2004, 17 patients with operable vulvar cancer situated on, or close to the midline were entered in a prospective study. All patients underwent sentinel node identification with (99m)Tc-labelled nanocolloid (preoperative lymphoscintigraphy and intraoperative use of a handheld probe). Depending on the surgeon, intraoperative blue dye was associated. Radical excision of the tumor and routine bilateral lymphadenectomy were then performed. Sentinel nodes were sent separately for histologic examination. Negative sentinel nodes on hematoxylin/eosine were further examined with immunohistochemistry. RESULTS: One or more sentinel nodes were identified in the 17 patients and in 21 of the 34 groins. In 5 patients, the sentinel nodes were metastatic. There was no false negative (negative sentinel node and metastatic non-sentinel node). In 13 patients, lymphoscintigraphy and then intraoperative identification suggested a unilateral drainage of the tumor with sentinel nodes localized in only one groin. Among these 13 patients, 3 groins with no sentinel node identified contained in fact massively metastatic nodes. CONCLUSION: Unilateral finding of a sentinel node in tumors of the midline does not preclude a metastatic node in the other groin. Lymph node assessment should remain bilateral in these lesions.

Assessment of myocardial reperfusion after myocardial infarction using automatic 3-dimensional quantification and template matching.

UNLABELLED: Assessment of perfusion defect extent is essential for determining prognosis after a myocardial infarction (MI), but quantification methods usually rely on segmental analysis, which may lack accuracy. We present an automated voxel-based and template-based approach for precise quantification of perfusion defect extent and reperfusion evolution. METHODS: Coronary angiography and stress/reinjection (201)Tl tomography were performed prospectively on 49 patients with recent MI (45 men; mean age +/- SD, 54 +/- 10 y), before and 3 mo after revascularization (40 angioplasties and 9 bypasses). Perfusion defect extent was quantified using expert 16-segment visual scoring of the slices and a 3-dimensional (3D) method with spatial normalization between times 1 and 2. Briefly, the latter automatically extracted myocardial edges, matched them to a reference template, and compared the perfusion intensity in each voxel with the intensity of the corresponding voxel in a control population of 100 healthy subjects. RESULTS: Reocclusion occurred in 12 patients within 3 mo of surgery (all had undergone angioplasty). The perfusion gain between times 1 and 2, assessed by visual analysis, was significantly higher in permeable patients than in reoccluded patients: 12.4% +/- 13.3% and 2.3% +/- 8.2% of the initial stress defect, respectively (P = 0.02). Proportional gains, measured with the quantitative 3D method, were 4.5% +/- 3.6% and 1.9% +/- 2.7%, respectively (P = 0.02). Furthermore, the 3D method allowed measurement within the initial ischemic defect (reversible part of the stress defect at time 1), the extent of myocardium whose perfusion improved at time 2 (reperfusion), and the extent of myocardium whose perfusion remained unchanged (residual ischemia). A voxel-by-voxel analysis of these regions revealed that the proportion of reperfusion was significantly higher in permeable patients than in reoccluded patients: 60.0% +/- 21.3% versus 40.0% +/- 22.5%, respectively (P = 0.008). This was cumbersome to quantify using visual analysis and did not reach statistical significance, likely because of segmental division (partial-volume effect) and absence of spatial normalization. CONCLUSION: The 3D voxel-based quantification allows satisfying assessment of reperfusion 3 mo after MI. Moreover, the automated analysis using spatial normalization should facilitate a reproducible assessment of large populations over time.

Diagnostic value of 99mTc-HMDP bone scan in atypical osseous tuberculosis mimicking multiple secondary metastases.

STUDY DESIGN: A case of atypical osseous tuberculosis (TB) mimicking multiple secondary metastases on radiologic and nuclear imaging is presented. OBJECTIVES: To emphasize the contribution of nuclear bone scanning for the assessment of osseous tuberculosis in typical and atypical presentations. SUMMARY AND BACKGROUND DATA: Skeletal locations of TB mostly involve the dorsolumbar spine and diagnosis is often delayed. The presence of multiple TB sites can mimic secondary metastases and biopsy remains the mainstay for final diagnosis. METHODS: Clinical symptoms, lab tests, and imaging data are presented. Possible diagnoses are discussed. A review of imaging characteristics in cases of typical and atypical presentations of osseous TB is proposed. RESULTS: A dorsal spine spondylitis was first diagnosed on a 56-year-old patient presenting neurologic deficit of the left arm. Fine needle aspiration identified bacterial infection but was negative for Mycobacterium tuberculosis. Whole-body bone scan allowed the identification of an asymptomatic sacroiliac lesion, which was accessible to biopsy and gave a final diagnosis. CONCLUSION: Nuclear bone scanning should be kept in mind when assessing spinal pain in patients at high risk of TB infection or reactivation.

Quantitative lung perfusion scan as a predictor of aerosol distribution heterogeneity and disease severity in children with cystic fibrosis.

BACKGROUND: The assessment of lung ventilation by radionuclide imaging has proved useful for the optimization of aerosol therapy in children with cystic fibrosis. Further analysis of lung perfusion may provide additional information. METHODS: Quantitative analysis of regional lung aerosol distribution (Tc phytates) and perfusion (Tc macroaggregates) homogeneity was performed in 18 children with cystic fibrosis, using the third and fourth spatial moments (skew and Kurtosis) of count distribution. Patients were chosen from a prospective study whose goal was to compare the efficacy of two nebulization methods of a radiolabelled aerosol: one session involved a nebulizer activated by patient inspiratory flow (control session), whereas the other involved a nebulizer powered by a pressure support device (PS session). RESULTS: Quantitative regional distribution of perfusion was similar to aerosol distribution, although skew and Kurtosis were lower, indicating better homogeneity. Perfusion skew was inversely correlated with pulmonary volumes and Shwachman score, even more significantly than ventilation skew. Using receiver operating characteristic curve analysis, a perfusion skew threshold of 0.67 was predictive of disease severity (FEV1 > or =60% or FEV1 <60%) with 86% sensitivity and 91% specificity. Furthermore, same skew threshold allowed the identification of patients who were 'PS responders' (greater amount of radioactivity deposited after the PS session) or 'PS non-responders' with 80% sensitivity and 77% specificity. CONCLUSION: Quantification of regional lung perfusion is easy to perform and heterogeneity of the distribution is closely correlated to disease severity. Moreover, perfusion skew can identify patients who are likely to benefit from pressure support (to optimize aerosol therapy) and may be helpful for orienting potential non-responders towards alternative therapies.