Pseudoprogression after proton beam irradiation for a choroid plexus carcinoma in pediatric patient: MRI and PET imaging patterns

Purpose: Pseudoprogression is a rare complication of radiation therapy, and discrimination between true progression and pseudoprogression is of paramount importance for further medical care. We present a case of intra-axial pseudoprogression following complementary proton radiation therapy for a choroid plexus carcinoma in a child. We aim to highlight radiological patterns of pseudoprogression after proton beam therapy. Case report: A 6-year-old girl presented with choroid plexus carcinoma, manifesting as change in behavior, tremor, and balance disorder. Partial resection and chemotherapy were performed. Complementary localized proton beam therapy (54Gy) was administered on the residual tumor. Eight month follow-up MRI showed an abnormal, irregular, rim-like enhancement in the pons and both temporal lobes within the field of irradiation. These lesions had a low cerebral blood volume (CBV) on perfusion MR imaging and no restricted diffusion. However, the lesions were hypermetabolic on O-(2-[18F]fluoroethyl)-l-tyrosine (FET)-PET MRI. Follow-up MRI showed disappearance of these lesions confirming the perfusion MR diagnosis of pseudoprogression. Conclusion: Based on this case, radiological patterns of pseudoprogression after proton beam therapy may be a low CBV and no restricted diffusion. Lesions can be hypermetabolic on FET-PET imagin

Scan without evidence of dopaminergic deficit: A 10-year retrospective study

123I-ioflupane SPECT is a powerful method to assess nigrostriatal dopamine system integrity. Several independent studies have shown that 1–15% of patients with suspected degenerative parkinsonism, mainly PD, have scans without evidence of dopaminergic deficit (SWEDD). It has been proposed that most SWEDD patients either present with a non-degenerative condition mimicking PD, such as atypical tremor or dystonia, or demonstrate an abnormal scan when repeated later. We here hypothesized that scan interpretation methods may also play a crucial yet underestimated role in this issue.Methods We previously established age-dependent reference values of striatal uptake by analyzing scans from a cohort of patients with non-degenerative conditions. We then studied a large population with well-established degenerative parkinsonism (N = 410, 80% with PD), using identical imaging protocol, to evaluate the prevalence of patients with normal scans based on routine visual assessment. Each scan was eventually reassessed using the same automated method as for controls and a detailed 3D analysis.Results Ten potential SWEDD cases (2.4%) were identified. However, both reassessment methods independently showed that these scans were all outside reference limits and/or visually abnormal when reexamined carefully, except for one case (0.2%) with corticobasal syndrome.Conclusion SPECT misinterpretation emerges as an important contributor to the SWEDD population, suggesting that suspected SWEDD cases should prompt not only a serious diagnosis challenge but, equally important, a detailed scan reassessment. True SWEDD cases seem extremely rare in degenerative parkinsonism. We propose that the very concept of SWEDD is more confusing than helpful and should be definitely abandoned

Feeling of presence in dementia with Lewy bodies is related to reduced left frontoparietal metabolism.

Funder: University of CambridgeFeeling of presence (FOP) refers to the vivid sensation of a person's presence near oneself and is common in Dementia with Lewy Bodies (DLB). Based on previous observations on epileptic subjects, we hypothesized that DLB subjects with FOP would harbour 18F-fluorodeoxyglucose PET hypometabolism in left parietal areas. 25 subjects (mean age 71.9 ± 6.7, disease duration at scan 1.7 ± 1.5 years) were included in the study, of whom nine (36%) experienced FOP. No significant between-group difference was observed regarding dopamine transporters striatal uptake (p = 0.64), daily dopaminergic treatment dosage (p = 0.88) and visual hallucinations (p = 0.83). Statistical parametric mapping showed that subjects with FOP had a significantly reduced glucose metabolism in several left frontoparietal areas (p < 0.001), including superior parietal lobule and precuneus. Interregional correlation analysis of these areas showed specific connectivity with right insula and putamen in the FOP subgroup and right orbitofrontal and superior frontal in subjects without FOP. This provides further evidence about the role of a left frontoparietal network and suggest a possible contribution of impaired orbitofrontal reality filtering associated with FOP

Projection Space Implementation of Deep Learning-Guided Low-Dose Brain PET Imaging Improves Performance over Implementation in Image Space

Purpose: To assess the performance of full dose (FD) positron emission tomography (PET) image synthesis in both image and projection space from low-dose (LD) PET images/sinograms without sacrificing diagnostic quality using deep learning techniques. Methods: Clinical brain PET/CT studies of 140 patients were retrospectively employed for LD to FD PET conversion. 5% of the events were randomly selected from the FD list-mode PET data to simulate a realistic LD acquisition. A modified 3D U-Net model was implemented to predict FD sinograms in the projection-space (PSS) and FD images in image-space (PIS) from their corresponding LD sinograms/images, respectively. The quality of the predicted PET images was assessed by two nuclear medicine specialists using a five-point grading scheme. Quantitative analysis using established metrics including the peak signal-to-noise ratio (PSNR), structural similarity index metric (SSIM), region-wise standardized uptake value (SUV) bias, as well as first-, second- and high-order texture radiomic features in 83 brain regions for the test and evaluation dataset was also performed. Results: All PSS images were scored 4 or higher (good to excellent) by the nuclear medicine specialists. PSNR and SSIM values of 0.96 ± 0.03, 0.97 ± 0.02 and 31.70 ± 0.75, 37.30 ± 0.71 were obtained for PIS and PSS, respectively. The average SUV bias calculated over all brain regions was 0.24 ± 0.96% and 1.05 ± 1.44% for PSS and PIS, respectively. The Bland-Altman plots reported the lowest SUV bias (0.02) and variance (95% CI: -0.92, +0.84) for PSS compared with the reference FD images. The relative error of the homogeneity radiomic feature belonging to the Grey Level Co-occurrence Matrix category was -1.07 ± 1.77 and 0.28 ± 1.4 for PIS and PSS, respectively Conclusion: The qualitative assessment and quantitative analysis demonstrated that the FD PET prediction in projection space led to superior performance, resulting in higher image quality and lower SUV bias and variance compared to FD PET prediction in the image domain

Distinct spatiotemporal patterns for disease duration and stage in Parkinson’s disease

Purpose: To assess correlations between the degree of dopaminergic depletion measured using single-photon emission computed tomography (SPECT) and different clinical parameters of disease progression in Parkinson’s disease (PD).Methods: This retrospective study included 970 consecutive patients undergoing ¹²³I-ioflupane SPECT scans in our institution between 2003 and 2013, from which we selected a study population of 411 patients according to their clinical diagnosis: 301 patients with PD (69.4 ± 11.0 years, of age, 163 men) and 110 patients with nondegenerative conditions included as controls (72.7 ± 8.0 years of age, 55 men). Comprehensive and operator-independent data analysis included spatial normalization into standard space, estimation of the mean uptake values in the striatum (caudate nucleus + putamen) and voxel-wise correlation between SPECT signal intensity and disease stage as well as disease duration in order to investigate the spatiotemporal pattern of the dopaminergic nigrostriatal degeneration. To compensate for potential interactions between disease stage and disease duration, one parameter was used as nonexplanatory coregressor for the other.Results: Increasing disease stage was associated with an exponential decrease in ¹²³I-ioflupane uptake (R ²  = 0.1501) particularly in the head of the ipsilateral caudate nucleus (p p R ²  = 0.1532) particularly in the contralateral anterior putamen (p < 0.0001).Conclusion: We observed two distinct spatiotemporal patterns of posterior to anterior dopaminergic depletion associated with disease stage and disease duration in patients with PD. The developed operator-independent reference database of 411 ¹²³I-ioflupane SPECT scans can be used for clinical and research applications

Establishing on-site reference values for 123I-FP-CIT SPECT (DaTSCAN®) using a cohort of individuals with non-degenerative conditions

To overcome the issue of reference values for DaTSCAN® requiring healthy controls, we propose an original approach using scans from individuals with non- degenerative conditions performed at one single center following the same acquisition protocol. Procedures: From a cohort of 970 consecutive patients, we identified 182 patients with a clinical diagnosis of non-degenerative parkinsonism or tremor and a visually normal DATSCAN®. Caudate nucleus (C), putamen (P), and striatum (S) uptake values, C/P ratios, and asymmetry indexes (AI) were calculated using semi-quantitative methods. Outcomes were assessed according to age and gender, and reference limits were established using the percentile approach. Results: A significant negative linear effect of age was found upon striatal nuclei uptake of 0.21–0.22 per decade (6.8 %/decade for striatum), whereas a potential gender influence proved unclear. Inferior reference limits were established at the 5th percentile. C/P ratios and AIs were not influenced by age or gender, and superior reference limits were set at the 95th percentile. Conclusions: We here propose a convenient approach to calculate site-specific reference limits for DaTSCAN® outcomes not requiring scanning healthy controls. The method appears to yield robust values that range within nearly identical limits as those obtained in healthy subjects

Extrastriatal 123I-FP-CIT SPECT impairment in Parkinson's disease - the PPMI cohort.

BACKGROUND: Neuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson's disease (PD). We undertook a case-controlled analysis of 123I-FP-CIT SPECT images to measure extrastriatal serotonergic transporters (SERT) in PD using the Parkinson's Progression Markers Initiative (PPMI) cohort. METHODS: We included all PD (n = 154) and Control subjects (n = 62) with available 123I-FP-CIT SPECT imaging and high-resolution T1-weighted MRI for coregistration (PD: mean age 61.6 years, 62% male, disease duration 26 months, MDS-UPDRS III score 22). 123I-FP-CIT SPECT images were processed with PETPVE12 using an exploratory voxel-wise analysis including partial-volume effect correction. Linear regressions were performed in the PD group to assess correlations between region of interest 123I-FP-CIT uptake and clinical motor and non-motor impairment. RESULTS: Compared to Controls, PD exhibited an uptake reduction in bilateral caudate nucleus, putamen, insula, amygdala and right pallidum (family-wise error (FWE)-corrected p  0.45) or excessive daytime sleepiness (all p > 0.29). CONCLUSIONS: In addition to the well-established striatal deficit, this study provides evidence of a major extrastriatal 123I-FP-CIT impairment, and therefore of an altered serotonergic transmission in early PD

Radiologic Patterns of Necrosis After Proton Therapy of Skull Base Tumors

Background: Discrimination between radiation necrosis and tumor progression after radiation therapy represents a radiologic challenge. The aim of our investigation is to identify patterns of radiation necrosis on brain magnetic resonance imaging (MRI) and positron emission tomography (PET) with Fluoroethyltyrosin (FET) after proton beam therapy (PBT) for skull base tumors. Material and Methods: Five consecutive patients with extra-axial neoplasms were included, presenting a total of eight radiation necrosis lesions (three clival chordomas; two petroclival chondrosarcomas; two women; mean age: 49 ± 18.2 years). Radiation necrosis was defined as the appearance of abnormal enhancement on MRI after PBT decreasing over time, and additional histopathologic confirmation in one patient. MRI and PET imaging were retrospectively analyzed by two experienced radiologists in consensus. Results: All lesions were localized close to the primary tumor in the field of irradiation. Three patients showed bilateral symmetrical lesions. All lesions showed T2 hyperintensity and T1 hypointensity. Cerebral blood volume (CBV) was reduced in all available studies. None of the lesions showed a restricted diffusion. FET-PET (three patients) showed a higher uptake in four out of five lesions; three of which had a mean tumor-to-background (TBRmean) uptake lower than 1.95 and FET uptake increasing over time and were correctly classified into radiation necrosis. Conclusions: Most radiation necroses were in direct continuity with the primary tumor mimicking tumor progression. The most consistent imaging findings for PBT radiation necrosis are low CBV without restricted diffusion and FET-PET TBRmean lower than 1.95 or increasing uptake over time. Bilateral symmetric involvement may be another indicator of radiation necrosi

Manual and semi-automated approaches to MIBG myocardial scintigraphy in patients with Parkinson’s disease

OBJECTIVE: This study investigates the effects of manual and semi-automatic methods for assessing MIBG semi-quantitative indices in a clinical setting. MATERIALS AND METHODS: We included (123)I-MIBG scans obtained in 35 patients with idiopathic Parkinson’s Disease. Early and late heart-to-mediastinum (H/M) ratios were calculated from (123)I-MIBG images using regions of interest (ROIs) placed over the heart and the mediastinum. The ROIs were derived using two approaches: (i) manually drawn and (ii) semi-automatic fixed-size ROIs using anatomical landmarks. Expert, moderate-expert, and not expert raters applied the ROIs procedures and interpreted the (123)I-MIBG images. We evaluated the inter and intra-rater agreements in assessing (123)I-MIBG H/M ratios. RESULTS: A moderate agreement in the raters’ classification of pathological and non-pathological scores emerged regarding early and late H/M ratio values (κ = 0.45 and 0.69 respectively), applying the manual method, while the early and late H/M ratios obtained with the semi-automatic method reached a good agreement among observers (κ = 0.78). Cohen-Kappa values revealed that the semi-automatic method improved the agreement between expert and inexpert raters: the agreement improved from a minimum of 0.29 (fair, for early H/M) and 0.69 (substantial, in late H/M) with the manual method, to 0.90 (perfect, in early H/M) and 0.87 (perfect, in late H/M) with the semi-automatic method. CONCLUSION: The use of the semi-automatic method improves the agreement among raters in classifying’ H/M ratios as pathological or non-pathological, namely for inexpert readers. These results have important implications for semi-quantitative assessment of (123)I-MIBG images in clinical routine

White matter changes in corticobasal degeneration syndrome and correlation with limb apraxia

BACKGROUND: Data on white matter changes in corticobasal degeneration syndrome (CBDS) are not yet available, whereas cortical gray matter loss is a feature of this condition. The structural abnormalities related to a key feature of CBDS (limb apraxia) are unknown. OBJECTIVES: To measure selective structural changes in early CBDS using diffusion tensor imaging and voxel-based morphometry and to evaluate the structural correlates of limb apraxia. DESIGN: Patient and control group comparison. SETTING: Referral center for dementia and movement disorders. PARTICIPANTS: Twenty patients with CBDS and 21 matched control subjects. INTERVENTIONS: Clinical and standardized neuropsychological evaluations, including assessment of limb apraxia. MAIN OUTCOME MEASURES: Gray and white matter changes in early CBDS. RESULTS: Diffusion tensor imaging revealed decreases in fractional anisotropy in the long frontoparietal connecting tracts, the intraparietal associative fibers, and the corpus callosum. Fractional anisotropy was also reduced in the sensorimotor projections of the cortical hand areas. Voxel-based morphometry showed a prevalent gray matter reduction in the left hemisphere (in the inferior frontal and premotor cortices, parietal operculum, superotemporal gyrus, and hippocampus). The pulvinar, bilaterally, and the right cerebellar cortex also showed atrophy. Limb apraxia correlated with parietal atrophy and with fractional anisotropy reductions in the parietofrontal associative fibers (P < .01). The limb-kinetic component of apraxia correlated with reduction of hand sensorimotor connecting fibers. CONCLUSIONS: The present integrative approach to in vivo structural anatomy combines hodologic imaging, describing patterns of white matter connections between cortical areas, with neuropsychological data. This provides new evidence of gray matter and fiber tract abnormalities in early-phase disease and contributes to clarifying the neural basis of apraxia in CBDS