FDG-PET/CT is a pivotal imaging modality to diagnose rare intravascular large B-cell lymphoma: case report and review of literature.

Intravascular large B-cell lymphoma (IVLBCL) remains a diagnostic challenge, because of non-specific findings on clinical, laboratory, and imaging studies. We present a case in which 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography was particularly useful to suspect the diagnosis, to detect unexpected locations, to guide contributive biopsy, and to assess the response to treatment. In case of initial negative results, FDG-PET should be repeated in the course of clinical evolution. In the presence of neurological or hormonal symptoms without brain magnetic resonance imaging abnormality, FDG-PET brain slices could depict additional pituitary and/or brain hypermetabolisms. We discuss the potential interests of FDG-PET in IVLBCL by a literature review.

Independent prognostic value of pre-treatment 18-FDG-PET in high-grade gliomas.

The prognostic value of PET with (18F)-fluoro-2-deoxy-D: -glucose (FDG) has been shown in high-grade gliomas (HGG), but not compared with consensual prognostic factors. We sought to evaluate the independent predictive value of pre-treatment FDG-PET on overall (OS) and event-free survival (EFS). We retrospectively analyzed 41 patients with histologically-confirmed HGG (31 glioblastomas and 10 anaplastic gliomas). The pre-treatment uptake of FDG was assessed qualitatively by five-step visual metabolic grading, and quantitatively by the ratio between the tumor and contralateral maximal standardized uptake value (T/CL). EFS and OS following PET were compared with FDG uptake by univariate analysis, and by two multivariate analyses: one including main consensual prognostic factors (age, KPS, extent of surgery and histological grade), and the other including the classification system of the Radiation Therapy Oncology Group (Recursive Partitioning Analysis, RPA). Median OS and EFS were 13.8 and 7.4 months, respectively, for glioblastomas, and over 25.8 and 12 months, respectively, for anaplastic gliomas (P = 0.040 and P = 0.027). The T/CL ratio predicted OS in the entire group [P = 0.003; Hazard Ratio (HR) = 2.3] and in the glioblastoma subgroup (P = 0.018; HR = 2), independently of age, Karnofsky performance status, histological grade, and surgery, and independently of RPA classification. T/CL ratio tended to predict EFS in the whole group (P = 0.052). The prognostic value of visual metabolic grade on OS was less significant than T/CL ratio, both in the entire group and in the glioblastoma subgroup (P = 0.077 and P = 0.059). Quantitative evaluation of the ratio between the maximal tumor and contralateral uptake in pre-treatment FDG-PET provides significant additional prognostic information in newly-diagnosed HGG, independently of consensual prognostic factors.

Predictive value of brain perfusion SPECT for rTMS response in pharmacoresistant depression.

PURPOSE: The aim of this study was to determine the predictive value of whole-brain voxel-based regional cerebral blood flow (rCBF) for repetitive transcranial magnetic stimulation (rTMS) response in patients with pharmacoresistant depression. METHODS: Thirty-three right-handed patients who met DSM-IV criteria for major depressive disorder (unipolar or bipolar depression) were included before rTMS. rTMS response was defined as at least 50% reduction in the baseline Beck Depression Inventory scores. The predictive value of (99m)Tc-ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) for rTMS response was studied before treatment by comparing rTMS responders to non-responders at voxel level using Statistical Parametric Mapping (SPM) (p < 0.001, uncorrected). RESULTS: Of the patients, 18 (54.5%) were responders to rTMS and 15 were non-responders (45.5%). There were no statistically significant differences in demographic and clinical characteristics (p > 0.10). In comparison to responders, non-responders showed significant hypoperfusions (p < 0.001, uncorrected) in the left medial and bilateral superior frontal cortices (BA10), the left uncus/parahippocampal cortex (BA20/BA35) and the right thalamus. The area under the curve for the combination of SPECT clusters to predict rTMS response was 0.89 (p < 0.001). Sensitivity, specificity, positive predictive value and negative predictive value for the combination of clusters were: 94, 73, 81 and 92%, respectively. CONCLUSION: This study shows that, in pharmacoresistant depression, pretreatment rCBF of specific brain regions is a strong predictor for response to rTMS in patients with homogeneous demographic/clinical features.

IDH mutation status impact on in vivo hypoxia biomarkers expression: new insights from a clinical, nuclear imaging and immunohistochemical study in 33 glioma patients.

Mutations in the gene encoding isocitrate dehydrogenase enzyme isoforms 1 (IDH1) and 2 (IDH2) have recently been identified in a large proportion of glial tumors of the CNS, but their mechanistic role in tumor development remains unclear. Here, we assessed the actual impact of IDH1 and IDH2 mutations in patients harboring WHO grade II and III gliomas. We sequenced IDH1 at codon 132 and IDH2 at codon 172 in 33 patients with WHO grade II and III gliomas who benefited from a preoperative (18)F-FDG positron emission tomography (PET). Immunohistochemical expression of Hypoxia Inducible Factor-1alpha (HIF-1α), Carbonic Anhydrase IX (CAIX), Glucose Transporter 1 (GLUT1) and Caspase 3 active form (CASP3) along with the R132HIDH1 mutation was assessed in all cases as well as 1p/19q deletion status and p53 expression. HIF-1α expression was found in 15% of IDH-mutated compared to 7.7% of IDH-nonmutated tumors (P = 0.954). Also, GLUT-1 positive staining was found in 5% of IDH-mutated and in 7.1% of IDH-nonmutated tumors (P = 0.794). Finally, CA-IX expression was found in 15% of IDH-mutated and in 7.7% of IDH-nonmutated tumors (P = 0.484). The combined expression of these three hypoxic markers was found in two WHO grade III tumors, one of which was IDH-mutated whereas the other was IDH-nonmutated (P = 0.794). In IDH-mutated tumors, the median SUVmax ratio was 2.24 versus 2.15 in IDH-nonmutated tumors (P = 0.775). Together, these data question the actual relationship between IDH mutation status and in vivo hypoxic biomarkers expression in WHO grade II and III gliomas.

Chocolate intake associated with failed labeling of (99m)Tc red blood cells.

UNLABELLED: Red blood cells (RBC) labeled in vivo with (99m)Tc-pertechnetate are used worldwide in nuclear medicine departments. METHODS: Here, we present a case of (99m)Tc-RBC labeling failure associated with chocolate intake in a 25-y-old woman, resulting in uninterpretable images. Because of this clinical observation, we performed in vitro RBC labeling on blood samples from volunteers after they consumed chocolate. RESULTS: Chocolate intake inhibited the labeling rate, compared with the control condition, and significantly increased the (99m)Tc free fraction (34.1% +/- 11.3% vs. 14.0% +/- 1.2%). CONCLUSION: We cannot explain how this interaction could occur, but cacao components are known to modulate red cell and plasma oxidoreductive status and to modify red cell membrane permeability and plasticity. Therefore, for patients who can be considered likely to consume chocolate, such as young patients, we recommend that they limit their consumption of chocolate for 12 h before RBC labeling.

Utility of FDG-PET/CT in the follow-up of neuroblastoma which became MIBG-negative.

We report on the case of a 10-month-old female infant with a metastatic neuroblastoma which became MIBG-negative at time of relapse. We discuss the different hypothesis associated with this particular outcome, and the potential utility of FDG-PET as an alternative to follow up the residual disease at this stage.

Tomoscintigraphy improves the determination of the embryologic origin of parathyroid adenomas, especially in apparently inferior glands: imaging features and surgical implications.

UNLABELLED: Identification of the embryologic origin of hyperfunctioning parathyroid adenomas in primary hyperparathyroidism (PHPT) could determine the most suitable approach for minimally invasive surgery. The aim of this study was to prospectively evaluate the reliability of a new, combined protocol for the preoperative localization and determination of the embryologic origin of parathyroid adenomas. METHODS: Anterior dual-isotope ((123)I/(99m)Tc-sestamibi) static planar imaging followed by tomoscintigraphy (SPECT acquisition) centered over the 140-keV photopeak (combined protocol) was performed on 35 consecutive patients with sporadic PHPT. On the basis of anatomic considerations, adenomas were classified as superior (P4 derived) if they were located above the isthmus or posterior to the thyroid on SPECT images, despite their apparently middle to inferior position, and as inferior (P3 derived) if the foci were located in inferior and anterior positions or along the thyrothymic tract. Parathyroid ultrasonography was performed on all patients. RESULTS: A total of 36 adenomas were removed: 34 solitary adenomas and 1 double adenoma (for totals of 19 P3-derived and 17 P4-derived adenomas). Pinhole subtraction imaging, SPECT, and ultrasonography sensitivities for detecting adenomas were 86%, 78%, and 77%, respectively. False-positive contralateral images were observed only with ultrasonography (3 cases). Positive SPECT results were associated with higher gland weights. Thirteen glands were identified by SPECT as posterior glands, despite their apparently inferior position, and were removed through an appropriate lateral endoscopic approach. Eleven (85%) of these glands had a P4 origin. Only 2 corresponded to large P3-derived adenomas (>2 g). CONCLUSION: By reclassifying apparently inferior adenomas as P4-derived adenomas prolapsed behind the thyroid gland, SPECT provides information about the most suitable surgical approach for avoiding recurrent laryngeal nerve injury. Additional pinhole images should increase the detection of small adenomas. The combined protocol offers both advantages.

Usefulness of 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography for staging and evaluation of treatment response in IgG4-related disease: a retrospective multicenter study.

OBJECTIVE: To evaluate the usefulness of 2-[18F]-fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in IgG4-related disease (IgG4-RD) for the staging of the disease and the followup under treatment. METHODS: All patients included in the French IgG4-RD registry who underwent ≥1 FDG-PET/CT scan were included in the study. Clinical, biologic, pathologic, radiologic, and FDG-PET/CT qualitative and quantitative findings were retrospectively collected and analyzed. RESULTS: Twenty-one patients were included in the study and 46 FDG-PET/CT examinations were evaluated. At either diagnosis or relapse, all evaluated patients presented abnormal 18F-FDG uptake in typical IgG4-RD localizations. In most cases, FDG-PET/CT was more sensitive than conventional imaging to detect organ involvement, especially in arteries, salivary glands, and lymph nodes. In few cases (small-sized lesions and brain or kidney contiguous lesions), false-negative results were noted. Evaluation before and after treatment showed in most cases a good correlation of FDG-PET/CT results with treatment response and disease activity. CONCLUSION: This large retrospective study shows that FDG-PET/CT imaging is useful for the staging of IgG4-RD. Moreover, FDG-PET/CT is useful to assess the response to treatment during followup.

FDG-PET predicts survival in recurrent high-grade gliomas treated with bevacizumab and irinotecan.

Prognosis of recurrent high-grade glioma (HGG) is poor, although bevacizumab has been documented in that context. This study aimed to determine the independent prognostic value of fluorodeoxyglucose (FDG)-PET on progression-free survival (PFS) and overall survival (OS) of recurrent HGG after combined treatment with bevacizumab and irinotecan, compared with other documented prognostic variables. Twenty-five adult patients with histologically proven HGG were included at recurrence. Brain FDG-PET imaging was performed within 6 weeks of starting chemotherapy with bevacizumab and irinotecan. Response based on MRI was assessed every 2 months according to revised assessment in Neuro-Oncology (RANO) criteria. Median PFS and OS were 4 months (range, 0.9-10.4 months) and 7.2 months (range, 1.2-41.7 months), respectively. At 6 months, PFS and OS rate were 16.0% and 72.0%. FDG uptake was the most powerful predictor of both PFS and OS, using either univariate or multivariate analysis, among all variables tested: histological grade, Karnofsky performance status, steroid intake, and number of previous treatments. Moreover, FDG uptake was also prognostic of response to bevacizumab-based therapy. This study provides the first evidence that pretreatment FDG-PET can serve as an imaging biomarker in recurrent HGG for predicting survival following anti-angiogenic therapy with bevacizumab.

Equivalent brain SPECT perfusion changes underlying therapeutic efficiency in pharmacoresistant depression using either high-frequency left or low-frequency right prefrontal rTMS.

BACKGROUND: Functional neuroimaging studies have suggested similar mechanisms underlying antidepressant effects of distinct therapeutics. OBJECTIVE: This study aimed to determine and compare functional brain patterns underlying the antidepressant response of 2 distinct protocols of repetitive transcranial magnetic stimulation (rTMS). METHODS: 99mTc-ECD SPECT was performed before and after rTMS of dorsolateral prefrontal cortex in 61 drug-resistant right-handed patients with major depression, using high frequency (10Hz) left-side stimulation in 33 patients, and low frequency (1Hz) right-side stimulation in 28 patients. Efficiency of rTMS response was defined as at least 50% reduction of the baseline Beck Depression Inventory score. We compared the whole-brain voxel-based brain SPECT changes in perfusion after rTMS, between responders and non-responders in the whole sample (p<0.005, uncorrected), and separately in the subgroup of patients with left- and right-stimulation. RESULTS: Before rTMS, the left- and right-prefrontal stimulation groups did not differ from clinical data and brain SPECT perfusion. rTMS efficiency (evaluated on % of responders) was statistically equivalent in the two groups of patients. In the whole-group of responder patients, a perfusion decrease was found after rTMS, in comparison to non-responders, within the left perirhinal cortex (BA35, BA36). This result was secondarily confirmed separately in the two subgroups, i.e. after either left stimulation (p=0.017) or right stimulation (p<0.001), without significant perfusion differences between these two subgroups. CONCLUSIONS: These data show that distinct successful rTMS protocols induce equivalent brain functional changes associated to antidepressive efficiency, consisting to a remote brain limbic activity decrease within the left perirhinal cortex. However, these results will have to be confirmed in a double-blind randomized trial using a sham control group.

FDG-PET to predict different patterns of progression in multicentric glioblastoma: a case report.

True multicentric glioblastoma multiforme (GBM) is rare and consists of separate distinct tumors in different cerebral lobes or hemispheres without any apparent route of dissemination. Few data are available describing its imaging using positron emission tomography (PET) with [18F]-fluoro-2-deoxy-D: -glucose (FDG). In this paper, we report on the case of a man with bifocal tumor in the right frontal and temporal lobes who underwent FDG-PET imaging. Visual and semiquantitative analysis showed two different metabolic patterns with much more intense uptake in the smaller temporal lesion. Subtotal surgical removal of the main frontal lesion allowed satisfactory control in the operative site, whereas the temporal lesion was rapidly progressive with occurrence of necrosis, which led to a second neurosurgery. The diagnosis of glioblastoma was confirmed by neuropathological examination in both cases but with much higher immunohistochemical expression of O(6)-methylguanine-DNA-methyltransferase (MGMT) in the temporal lesion. This report illustrates the potential interest of FDG-PET in multicentric GBMs to identify different metabolic patterns, in accordance with clinical, morphological, and molecular aggressiveness.

FDG PET and evaluation of posttherapeutic residual tumors in pediatric oncology: preliminary experience.

INTRODUCTION: Residual masses are an important problem in oncology. The determination of their nature (fibrosis or active tumor) is crucial. The place of 18F-fluorodeoxyglucose -positron emitting tomography (PET) as a new imaging device remains to be determined in this context. OBJECTIVES: To evaluate the place of 18F-fluorodeoxyglucose -PET in the prediction of the nature of residual masses in children with solid tumors. PATIENTS AND METHODS: Between January 2004 and January 2006, 238 PETs were performed in children followed up in the pediatric oncology and hematology departments. This was a monocentric retrospective review of the medical files of 18 children, in whom the main objective of the PET was to evaluate a residual mass. The sex ratio was 1/5; the median age 100 months (range, 34 to 180 mo). The underlying diseases were Hodgkin disease (n=5), lymphomas (n=5), osteosarcomas (n=3), rhabdomyosarcomas (n=2), and others (n=3). The final diagnostic (remission or persistent disease) was given by follow-up (median, 18 mo; range, 18 to 40), together with clinical, radiologic, and biopsy (in 6 cases) data. RESULTS: PET was negative in 13 cases and positive in 5, among them 4 patients relapsed. Among the 13 negative PETs, there was 1 relapse and 12 remissions. The respective value of PET sensibility and specificity were 0.8 and 0.92, respectively. Positive and negative predictive values were 0.8 and 0.92, respectively. CONCLUSION: On the basis of these preliminary results, PET seems to be an interesting tool to assess the nature of posttherapeutic residual masses in children, regardless of the underlying malignancy. Its role needs to be confirmed and further explored by multicentric studies tailored according to the underlying disease.

Predictive value of brain perfusion SPECT for ketamine response in hyperalgesic fibromyalgia.

PURPOSE: Ketamine has been used successfully in various proportions of fibromyalgia (FM) patients. However, the response to this specific treatment remains largely unpredictable. We evaluated brain SPECT perfusion before treatment with ketamine, using voxel-based analysis. The objective was to determine the predictive value of brain SPECT for ketamine response. METHODS: Seventeen women with FM (48 +/- 11 years; ACR criteria) were enrolled in the study. Brain SPECT was performed before any change was made in therapy in the pain care unit. We considered that a patient was a good responder to ketamine if the VAS score for pain decreased by at least 50% after treatment. A voxel-by-voxel group analysis was performed using SPM2, in comparison to a group of ten healthy women matched for age. RESULTS: The VAS score for pain was 81.8 +/- 4.2 before ketamine and 31.8 +/- 27.1 after ketamine. Eleven patients were considered "good responders" to ketamine. Responder and non-responder subgroups were similar in terms of pain intensity before ketamine. In comparison to responding patients and healthy subjects, non-responding patients exhibited a significant reduction in bilateral perfusion of the medial frontal gyrus. This cluster of hypoperfusion was highly predictive of non-response to ketamine (positive predictive value 100%, negative predictive value 91%). CONCLUSION: Brain perfusion SPECT may predict response to ketamine in hyperalgesic FM patients.

Follow-up of pain processing recovery after ketamine in hyperalgesic fibromyalgia patients using brain perfusion ECD-SPECT.

PURPOSE: The aim of this study was to determine whether the follow-up of pain processing recovery in hyperalgesic fibromyalgia (FM) could be objectively evaluated with brain perfusion ethyl cysteinate dimer single photon computerized tomography (ECD-SPECT) after administration of ketamine. MATERIALS AND METHODS: We enrolled 17 hyperalgesic FM women patients (48.5 +/- 11 years, range 25-63). After treatment with subcutaneous ketamine, 11 patients were considered as "good responders", with a decrease in pain intensity, evaluated by visual analog scale (VAS), greater than 50%. On the other hand, six patients were considered as "poor responders". A voxel-based analysis of regional cerebral blood flow (rCBF) was conducted (p (voxel) < 0.001uc), in the two subgroups of patients, before and after treatment, in comparison to a group of ten healthy subjects, matched for age and gender. RESULTS: In comparison to baseline brain SPECT, midbrain rCBF showed a greater increase after ketamine in the responder group than in the nonresponder group (p (cluster) = 0.016c). In agreement with the clinical response, the change in midbrain rCBF after ketamine was highly correlated with the reduction of VAS pain score (r = 0.7182; p = 0.0041). CONCLUSION: This prospective study suggests that blockade of facilitatory descending modulation of pain with ketamine can be evaluated in the periaqueductal grey with brain perfusion SPECT.