Michail Plotkin

Positron Emission Tomography for Staging of Pediatric Sarcoma Patients: Results of a Prospective Multicenter Trial

PURPOSE The objective of this study was to evaluate the impact of positron emission tomography (PET) using fluorine-18-fluorodeoxyglucose (FDG) for initial staging and therapy planning in pediatric sarcoma patients. PATIENTS AND METHODS In this prospective multicenter study, 46 pediatric patients (females, n = 22; males, n = 24; age range, 1 to 18 years) with histologically proven sarcoma (Ewing sarcoma family tumors, n = 23; osteosarcoma, n = 11; rhabdomyosarcoma, n = 12) were examined with conventional imaging modalities (CIMs), including ultrasound, computed tomography (CT), magnetic resonance imaging, and bone scintigraphy according to the standardized algorithms of the international therapy optimization trials, and whole-body FDG-PET. A lesion- and patient-based analysis of PET alone and CIMs alone and a side-by-side (SBS) analysis of FDG-PET and CIMs were performed. The standard of reference consisted of all imaging material, follow-up data (mean follow-up time, 24 +/- 12 months), and histopathology and was determined by an interdisciplinary tumor board. RESULTS FDG-PET and CIMs were equally effective in the detection of primary tumors (accuracy, 100%). PET was superior to CIMs concerning the correct detection of lymph node involvement (sensitivity, 95% v 25%, respectively) and bone manifestations (sensitivity, 90% v 57%, respectively), whereas CT was more reliable than FDG-PET in depicting lung metastases (sensitivity, 100% v 25%, respectively). The patient-based analysis revealed the best results for SBS, with 91% correct therapy decisions. This was significantly superior to CIMs (59%; P < .001). CONCLUSION In staging pediatric sarcoma, subsidiary FDG-PET scanning depicts important additional information and has a relevant impact on therapy planning when analyzed side-by-side with CIMs.

Combined 123I-FP-CIT and 123I-IBZM SPECT for the diagnosis of parkinsonian syndromes: study on 72 patients.

Summary.72 consecutive patients with suspected parkinsonian syndromes (PS) were studied by dopamine transporter (DAT) and D2 receptor SPECT in order to evaluate the accuracy of combined SPECT imaging. In the follow-up, the patients were diagnosed as having Parkinson’s disease (PD, n = 25), dementia with Lewy bodies (DLB, n = 6), multiple system atrophy (MSA, n = 13), progressive supranuclear palsy (PSP, n = 8), corticobasal degeneration (CBD, n = 9), and essential tremor (ET, n = 11). Using the iteratively estimated optimal cutoffs, DAT was reduced in 57/61 PS patients, whereas all ET patients were identified as “normal”. Reduced D2 receptor binding had 7/13 patients with MSA, 6/8 patients with PSP, 2/9 patients with CBD and no ET, PD or DLB patients. FP-CIT SPECT allows an accurate detection of nigrostriatal affection in neurodegenerative PS. IBZM SPECT is useful to approve the diagnosis of PSP and MSA although a normal finding cannot exclude an atypical PS. IBZM SPECT seems to be of restricted value in CBD.

Detection of Recurrent Pancreatic Cancer: Comparison of FDG-PET with CT/MRI

Objective: To determine the value of fluorine-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for the detection of recurrent pancreatic cancer in comparison to computed tomography (CT) and magnetic resonance imaging (MRI). Methods: Thirty-one patients with suspected recurrence after surgery were included. Inclusion criteria were sudden weight loss, pain or increased CA 19-9 levels. FDG-PET was performed in all patients. After visual analysis, maximal standardized uptake values (SUVmax) were determined by placing regions of interest on the pancreas bed. Additionally, all patients underwent contrast-enhanced multidetector CT (n = 14) or MR (n = 17) imaging. Positive findings at FDG-PET or CT/MRI were compared to follow-up. Results: All patients relapsed. Of 25 patients with local recurrences upon follow-up, initial imaging suggested relapse in 23 patients. Of these, FDG-PET detected 96% (22/23) and CT/MRI 39% (9/23). Local SUVmax ranged from 2.26 to 16.9 (mean, 6.06). Among 12 liver metastases, FDG-PET detected 42% (5/12). CT/MRI detected 92% (11/12) correctly. Moreover, 7/9 abdominal lesions were malignant upon follow-up of which FDG-PET detected 7/7 and CT/MR detected none. Additionally, FDG-PET detected extra-abdominal metastases in 2 patients. Conclusion: In patients suspected of pancreatic cancer relapse; FDG-PET reliably detected local recurrences, whereas CT/MRI was more sensitive for the detection of hepatic metastases. Furthermore, FDG-PET proved to be advantageous for the detection of nonlocoregional and extra-abdominal recurrences.

Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage A Correlative Microdialysis-PET Study

Background and Purpose— Cerebral microdialysis (MD) is discussed as a technique for detection of cerebral ischemia in subarachnoid hemorrhage; however, clinical data on cerebral blood flow (CBF) are limited in these patients. The main objective of this study was to investigate whether pathological MD parameters reflect a reduced regional CBF (rCBF) determined by 15O-H2O PET. Methods— Thirteen subarachnoid hemorrhage patients (age, 48.7±15.0 years; World Federation of Neurological Surgeons grade 1 to 5) were studied. Extracellular glucose, lactate, lactate/pyruvate (L/P) ratio, glutamate, and glycerol levels were analyzed hourly. rCBF was determined in the volume of interest of the MD catheter and all vascular territories. MD values were correlated to rCBF on the day of PET. Then, MD concentrations of asymptomatic versus ischemic phases (3-day medians) were analyzed. Results— In symptomatic patients (n=10), rCBF was significantly lower compared with controls (n=3, P =0.048). Glutamate correlated best with rCBF (r =−0.66; P =0.014), followed by glycerol (r =−0.62; P =0.021). The L/P ratio was most sensitive (0.82) and specific (1.0) in indicating symptoms of ischemia, but only during longer periods of ischemia. Conclusions— rCBF correlates best with glutamate, followed by glycerol, whereas the L/P ratio is sensitive only after longer periods of ischemia. Clinically relevant regional metabolic derangements occur already above an rCBF of 20 mL·100 g−1·min−1. Future research should focus on identifying alternative causes of metabolic derangement in subarachnoid hemorrhage patients and optimal treatment management in these patients.

Brain parenchyma sonography and 123I‐FP‐CIT SPECT in Parkinson's disease and essential tremor

We aimed to investigate the accuracy of transcranial brain parenchyma sonography (TCS) for differentiation between idiopathic Parkinsons disease (PD) and essential tremor (ET) in comparison to 123I‐FP‐CIT SPECT (FP‐CIT SPECT). Seventy‐four patients, in whom PD or ET was suspected on the basis of clinical criteria, were analyzed. The echogenicity of the substantia nigra (SN) and the striatal binding of dopamine transporters (DAT) were evaluated by TCS and FP‐CIT SPECT, respectively. Three patients were excluded due to an insufficient transtemporal bone window using TCS. Forty‐six and 25 patients were clinically classified as PD and ET. SPECT revealed a reduced DAT binding in 42 of all 71 included patients. Thirty‐six of the 42 patients with abnormal FP‐CIT SPECT findings had a pathological SN hyperechogenicity, whereas TCS findings in the remaining 6 patients were normal. In 27 of 29 patients with normal SPECT findings the SN echogenicity was regular. Referring to FP‐CIT SPECT, the sensitivity and specificity of TCS for detection of PD were 86 and 93%; the positive and negative predictive values were 95 and 82%, respectively. Sensitivity and specificity in detection of clinically diagnosed PD patients were 78 and 92% for TCS and 91 and 100% for FP‐CIT SPECT, respectively. In patients with pathological FP‐CIT SPECT and pathological TCS, the extent of SN hyperechogenicity did not correlate with the degree of reduction in dopamine transporter binding on the side opposite of the more affected limb. TCS allows a reliable differentiation of PD and ET. The TCS SN hyperechogenicity does not correlate with the extent of dopaminergic neuron degeneration.

123I-IMT SPECT and 1HMR-Spectroscopy at 3.0T in the Differential Diagnosis of Recurrent or Residual Gliomas: A Comparative Study

The aim of this investigation was to compare two current non-invasive modalities, single photon emission tomography (SPECT) using 123-iodine-α-methyl tyrosine (123I-IMT) and single-voxel proton magnetic resonance spectroscopy (1H-MRS) at 3.0 T, with regard to their ability to differentiate between residual/recurrent tumors and treatment-related changes in patients pretreated for glioma. The patient population comprised 25 patients in whom recurrent glioma was suspected based on MR imaging. SPECT imaging started 10 min after iv. injection of 300–370 MBq 123I-IMT and was performed using a triple-head system. The IMT uptake was calculated semiquantitatively using regions-of-interest. 1H-MRS was performed at 3.0 T using the single-volume point-resolved spectroscopy (PRESS) technique. Guided by MR imaging volumes-of-interest for spectroscopy were placed into the suspected lesions. Signal intensities of choline-containing compounds (Cho), creatine and phosphocreatine (Cr), and N-acetylaspartate (NAA) were obtained. When using the cut-off of 1.62 for 123I-IMT uptake, the sensitivity, specificity, and accuracy of the 123I-IMT SPECT were 95, 100 and 96%, respectively. For 1H-MRS, the sensitivity, specificity and accuracy were 89, 83 and 88%, respectively, based both on the metabolic ratios of Cho/Cr and Cho/NAA as tumor criterion with cut-off values of 1.11 and 1.17, respectively. In conclusion, 123I-IMT SPECT yielded more favorable results compared to 1H-MRS at distinguishing recurrent and/or residual glioma from post-therapeutic changes and may be particularly valuable when the evaluation of tumor extent is necessary.

Ventral Striatal Prediction Error Signaling is Associated with Dopamine Synthesis Capacity and Fluid Intelligence

Fluid intelligence represents the capacity for flexible problem solving and rapid behavioral adaptation. Rewards drive flexible behavioral adaptation, in part via a teaching signal expressed as reward prediction errors in the ventral striatum, which has been associated with phasic dopamine release in animal studies. We examined a sample of 28 healthy male adults using multimodal imaging and biological parametric mapping with (1) functional magnetic resonance imaging during a reversal learning task and (2) in a subsample of 17 subjects also with positron emission tomography using 6‐[18F]fluoro‐L‐DOPA to assess dopamine synthesis capacity. Fluid intelligence was measured using a battery of nine standard neuropsychological tests. Ventral striatal BOLD correlates of reward prediction errors were positively correlated with fluid intelligence and, in the right ventral striatum, also inversely correlated with dopamine synthesis capacity (FDOPA K  inapp ). When exploring aspects of fluid intelligence, we observed that prediction error signaling correlates with complex attention and reasoning. These findings indicate that individual differences in the capacity for flexible problem solving relate to ventral striatal activation during reward‐related learning, which in turn proved to be inversely associated with ventral striatal dopamine synthesis capacity. Hum Brain Mapp, 2013.

Implication of 2-18fluor-2-deoxyglucose positron emission tomography in the follow-up of Hürthle cell thyroid cancer.

The aim of this retrospective study was to investigate the value of positron emission tomography (PET) with 2-18fluor-2-deoxy-glucose (FDG) in the follow-up of Hürthle cell thyroid cancer (HTC), a rare variant of thyroid malignancies. FDG-PET studies were performed in 17 patients with HTC. In subgroup A (n = 13) PET was initiated because of an elevated thyroglobulin (Tg) level whereas in subgroup B (n = 4) the study was performed to evaluate suspect findings of morphologic imaging while Tg remained undetectable. Pathologically increased FDG uptake was found in all patients of subgroup A. In 10 studies, PET results were proven as true-positive either by surgery or by morphologic imaging. One study was false-positive. Final evaluation was not possible in two cases. In subgroup B, PET was true-negative in three and false-positive in one patient. For the detection of recurrent HTC by means of FDG-PET a meta-analysis including data of a multicenter study revealed an overall sensitivity of 92%, a specificity of 80%, a positive predictive value of 92%, and a negative predictive value of 80% while the accuracy was 89%. This study supports the efficiency of FDG-PET in the follow-up of HTC.

Assessment of histological response of paediatric bone sarcomas using FDG PET in comparison to morphological volume measurement and standardized MRI parameters

PurposeThe objective of this study was to evaluate positron emission tomography (PET) using 18F-fluoro-2-deoxy-D-glucose (FDG) in comparison to volumetry and standardized magnetic resonance imaging (MRI) parameters for the assessment of histological response in paediatric bone sarcoma patients.MethodsFDG PET and local MRI were performed in 27 paediatric sarcoma patients [Ewing sarcoma family of tumours (EWS), n = 16; osteosarcoma (OS), n = 11] prior to and after neoadjuvant chemotherapy before local tumour resection. Several parameters for assessment of response of the primary tumour to therapy by FDG PET and MRI were evaluated and compared with histopathological regression of the resected tumour as defined by Salzer-Kuntschik.ResultsFDG PET significantly discriminated responders from non-responders using the standardized uptake value (SUV) reduction and the absolute post-therapeutic SUV (SUV2) in the entire patient population (∆SUV, p = 0.005; SUV2, p = 0.011) as well as in the subgroup of OS patients (∆SUV, p = 0.009; SUV2, p = 0.028), but not in the EWS subgroup. The volume reduction measured by MRI/CT did not significantly discriminate responders from non-responders either in the entire population (p = 0.170) or in both subgroups (EWS, p = 0.950; OS, p = 1.000). The other MRI parameters alone or in combination were unreliable and did not improve the results. Comparing diagnostic parameters of FDG PET and local MRI, metabolic imaging showed high superiority in the subgroup of OS patients, while similar results were observed in the population of EWS.ConclusionFDG PET appears to be a useful tool for non-invasive response assessment in the group of OS patients and is superior to MRI. In EWS patients, however, neither FDG PET nor volumetry or standardized MRI criteria enabled a reliable response assessment to be made after neoadjuvant treatment.

Brain tumor perfusion: Comparison of dynamic contrast enhanced magnetic resonance imaging using T1, T2, and T 2 * contrast, pulsed arterial spin labeling, and H215O positron emission tomography

OBJECTIVES Different techniques for measuring of perfusion are clinically available, but these are usually applied to healthy brain tissue. MATERIAL AND METHODS Five different techniques were used here in 12 patients with brain tumors to investigate the impact of tumor vascularization on the perfusion signal: three qualitative dynamic contrast-enhanced/susceptibility-contrast magnetic resonance imaging (DCE-MRI/DSC-MRI) techniques exploiting T(1), T(2), T(2)(*) contrast, and two quantitative techniques, pulsed arterial spin labeling (PASL) and H(2)(15)O positron emission tomography (H(2)(15)O-PET). RESULTS In a first approximation, a linear correlation was found between all five imaging modalities regarding the perfusion signal of both, normal brain tissue and tumor. The estimated values for tumor perfusion differed significantly between the techniques (1=methodical mean in arbitrary units): PASL: 0.83, H(2)(15)O-PET: 0.62, T(1)-DCE: 1.73, T(2)-DCE: 0.69, T(2)(*)-DSC: 0.89. CONCLUSIONS The tumor perfusion values, determined with different techniques are not comparable. The T(2)(*)-DSC, here applied with contrast agent presaturation of extravascular space, and PASL depict median perfusion most reliably.