Optimization and impact of sensitivity mode on abbreviated scan protocols with population-based input function for parametric imaging of [18F]-FDG for a long axial FOV PET scanner.

BACKGROUND: The long axial field of view, combined with the high sensitivity of the Biograph Vision Quadra PET/CT scanner enables the precise deviation of an image derived input function (IDIF) required for parametric imaging. Traditionally, this requires an hour-long dynamic PET scan for [18F]-FDG, which can be significantly reduced by using a population-based input function (PBIF). In this study, we expand these examinations and include the scanner's ultra-high sensitivity (UHS) mode in comparison to the high sensitivity (HS) mode and evaluate the potential for further shortening of the scan time. METHODS: Patlak Ki and DV estimates were determined by the indirect and direct Patlak methods using dynamic [18F]-FDG data of 6 oncological patients with 26 lesions (0-65 min p.i.). Both sensitivity modes for different number/duration of PET data frames were compared, together with the potential of using abbreviated scan durations of 20, 15 and 10 min by using a PBIF. The differences in parametric images and tumour-to-background ratio (TBR) due to the shorter scans using the PBIF method and between the sensitivity modes were assessed. RESULTS: A difference of 3.4 ± 7.0% (Ki) and 1.2 ± 2.6% (DV) was found between both sensitivity modes using indirect Patlak and the full IDIF (0-65 min). For the abbreviated protocols and indirect Patlak, the UHS mode resulted in a lower bias and higher precision, e.g., 45-65 min p.i. 3.8 ± 4.4% (UHS) and 6.4 ± 8.9% (HS), allowing shorter scan protocols, e.g. 50-65 min p.i. 4.4 ± 11.2% (UHS) instead of 7.3 ± 20.0% (HS). The variation of Ki and DV estimates for both Patlak methods was comparable, e.g., UHS mode 3.8 ± 4.4% and 2.7 ± 3.4% (Ki) and 14.4 ± 2.7% and 18.1 ± 7.5% (DV) for indirect and direct Patlak, respectively. Only a minor impact of the number of Patlak frames was observed for both sensitivity modes and Patlak methods. The TBR obtained with direct Patlak and PBIF was not affected by the sensitivity mode, was higher than that derived from the SUV image (6.2 ± 3.1) and degraded from 20.2 ± 12.0 (20 min) to 10.6 ± 5.4 (15 min). Ki and DV estimate images showed good agreement (UHS mode, RC: 6.9 ± 2.3% (Ki), 0.1 ± 3.1% (DV), peak signal-to-noise ratio (PSNR): 64.5 ± 3.3 dB (Ki), 61.2 ± 10.6 dB (DV)) even for abbreviated scan protocols of 50-65 min p.i. CONCLUSIONS: Both sensitivity modes provide comparable results for the full 65 min dynamic scans and abbreviated scans using the direct Patlak reconstruction method, with good Ki and DV estimates for 15 min short scans. For the indirect Patlak approach the UHS mode improved the Ki estimates for the abbreviated scans.

Prediction of synchronous distant metastasis of primary pancreatic ductal adenocarcinoma using the radiomics features derived from 18F-FDG PET and MRI.

AIM: To explore the potential of the joint radiomics analysis of positron-emission tomography (PET) and magnetic resonance imaging (MRI) of primary tumours for predicting the risk of synchronous distant metastasis (SDM) in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: 18F-FDG PET and MRI images of PDAC patients from January 2011 to December 2020 were collected retrospectively. Patients (n=66) who received 18F-FDG PET/CT and MRI were included in a development group. Patients (n=25) scanned with hybrid PET/MRI were incorporated in an external test group. A radiomics signature was constructed using the least absolute shrinkage and selection operator algorithm to select PET-MRI radiomics features of primary PDAC tumours. A radiomics nomogram was developed by combining the radiomics signature and important clinical indicators using univariate and multivariate analysis to assess patients' metastasis risk. The nomogram was verified with the employment of an external test group. RESULTS: Regarding the development cohort, the radiomics nomogram was found to be better for predicting the risk of distant metastasis (area under the curve [AUC]: 0.93, sensitivity: 87%, specificity: 85%) than the clinical model (AUC: 0.70, p<0.001; sensitivity:70%, specificity: 65%) and the radiomics signature (AUC: 0.89, p>0.05; sensitivity: 65%, specificity:100%). Concerning the external test cohort, the radiomics nomogram yielded an AUC of 0.85. CONCLUSION: PET-MRI based radiomics analysis exhibited effective prediction of the risk of SDM for preoperative PDAC patients and may offer complementary information and provide hints for cancer staging.

A deep neural network for parametric image reconstruction on a large axial field-of-view PET.

PURPOSE: The PET scanners with long axial field of view (AFOV) having ~ 20 times higher sensitivity than conventional scanners provide new opportunities for enhanced parametric imaging but suffer from the dramatically increased volume and complexity of dynamic data. This study reconstructed a high-quality direct Patlak Ki image from five-frame sinograms without input function by a deep learning framework based on DeepPET to explore the potential of artificial intelligence reducing the acquisition time and the dependence of input function in parametric imaging. METHODS: This study was implemented on a large AFOV PET/CT scanner (Biograph Vision Quadra) and twenty patients were recruited with 18F-fluorodeoxyglucose (18F-FDG) dynamic scans. During training and testing of the proposed deep learning framework, the last five-frame (25 min, 40-65 min post-injection) sinograms were set as input and the reconstructed Patlak Ki images by a nested EM algorithm on the vendor were set as ground truth. To evaluate the image quality of predicted Ki images, mean square error (MSE), peak signal-to-noise ratio (PSNR), and structural similarity index measure (SSIM) were calculated. Meanwhile, a linear regression process was applied between predicted and true Ki means on avid malignant lesions and tumor volume of interests (VOIs). RESULTS: In the testing phase, the proposed method achieved excellent MSE of less than 0.03%, high SSIM, and PSNR of ~ 0.98 and ~ 38 dB, respectively. Moreover, there was a high correlation (DeepPET: [Formula: see text]= 0.73, self-attention DeepPET: [Formula: see text]=0.82) between predicted Ki and traditionally reconstructed Patlak Ki means over eleven lesions. CONCLUSIONS: The results show that the deep learning-based method produced high-quality parametric images from small frames of projection data without input function. It has much potential to address the dilemma of the long scan time and dependency on input function that still hamper the clinical translation of dynamic PET.

Concept Development of an On-Chip PET System.

Organs-on-Chips (OOCs), microdevices mimicking in vivo organs, find growing applications in disease modeling and drug discovery. With the increasing number of uses comes a strong demand for imaging capabilities of OOCs. Positron Emission Tomography (PET) would be ideal for OOC imaging, however, current PET systems have insufficient spatial resolution for this task. In this work, we propose the concept of an On-Chip PET system capable of imaging OOCs. Our system consists of four detectors arranged around the OOC device. Each detector is made of two monolithic Lutetium-yttrium oxyorthosilicate (LYSO) crystals and covered with Silicon photomultipliers (SiPMs) on multiple surfaces. We use a Convolutional Neural Network (CNN) trained with data from a Monte Carlo Simulation (MCS) to predict the first gamma-ray interaction position inside the detector from the light patterns that are recorded by the SiPMs on the detector's surfaces. With the Line of Responses (LORs) created by the predicted interaction positions, we reconstruct with Simultaneous Algebraic Reconstruction Technique (SART). The CNN achieves a mean average prediction error of 0.78 mm in the best configuration. We use the trained network to reconstruct an image of a grid of 21 point sources spread across the field-of-view and obtain a mean spatial resolution of 0.53 mm. We demonstrate that it is possible to achieve a spatial resolution of almost 0.5 mm in a PET system made of multiple monolithic LYSO crystals by directly predicting the scintillation position from light patterns created with SiPMs. We observe that CNNs from the ResNet family perform better than those from the EfficientNet family and that certain surfaces encode significantly more information for the scintillation-point prediction than others.

Deep Learning for Predicting Gamma-Ray Interaction Positions in LYSO Detector.

Positron Emission Tomography (PET) is among the most commonly used medical imaging modalities in clinical practice, especially for oncological applications. In contrast to conventional imaging modalities like X-ray Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), PET retrieves in vivo information about biochemical processes rather than just anatomical structures. However, physical limitations and detector constraints lead to an order of magnitude lower spatial resolution in PET images. In recent years, the use of monolithic detector crystals has been investigated to overcome some of the factors limiting spatial resolution. The key to increasing PET systems' resolution is to estimate the gamma-ray interaction position in the detector as precisely as possible.In this work, we evaluate a Convolutional Neural Network (CNN) based reconstruction algorithm that predicts the gamma-ray interaction position using light patterns recorded with Silicon photomultipliers (SiPMs) on the crystal's surfaces. The algorithm is trained on data from a Monte Carlo Simulation (MCS) that models a gamma point source and a detector consisting of Lutetium-yttrium oxyorthosilicate (LYSO) crystals and SiPMs added to five surfaces. The final Mean Absolute Error (MAE) on the test dataset is 1.48 mm.

[Prostate-specific membrane antigen (PSMA)-based diagnostics and treatment of prostate cancer]. / Prostataspezifische Membranantigen(PSMA)-basierte Diagnostik und Therapie des Prostatakarzinoms.

BACKGROUND: Since their clinical introduction in 2011, PSMA-PET/CT (PSMA: prostate-specific membrane antigen) as well as PSMA therapy of prostate cancer (PC) have spread rapidly worldwide. OBJECTIVES: To summarize the current knowledge about both PSMA-PET/CT and PSMA therapy of PC. METHODS: The knowledge derived from the literature as well as the authors' experiences were collected in this review. RESULTS: PSMA-PET/CT demonstrates a very high sensitivity and specificity for the detection of recurrent PC as well as for the primary staging of intermediate- and high-risk PC. PSMA therapy shows promising results in third-line treatment for patients with castration-resistant, metastatic PC. CONCLUSIONS: PSMA-PET/CT is meanwhile established as the gold standard for the detection of recurrent PC and is in the process of assuming the same role for primary staging of intermediate- to high-risk PC. PSMA therapy serves as a promising third-line therapy in an increasing number of centers.

[18F]-florbetaben PET/CT Imaging in the Alzheimer's Disease Mouse Model APPswe/PS1dE9.

BACKGROUND: Positron-emission-tomography (PET) using 18F labeled florbetaben allows noninvasive in vivo-assessment of amyloid-beta (Aß), a pathological hallmark of Alzheimer's disease (AD). In preclinical research, [18F]-florbetaben-PET has already been used to test the amyloid-lowering potential of new drugs, both in humans and in transgenic models of cerebral amyloidosis. The aim of this study was to characterize the spatial pattern of cerebral uptake of [18F]-florbetaben in the APPswe/ PS1dE9 mouse model of AD in comparison to histologically determined number and size of cerebral Aß plaques. METHODS: Both, APPswe/PS1dE9 and wild type mice at an age of 12 months were investigated by smallanimal PET/CT after intravenous injection of [18F]-florbetaben. High-resolution magnetic resonance imaging data were used for quantification of the PET data by volume of interest analysis. The standardized uptake values (SUVs) of [18F]-florbetaben in vivo as well as post mortem cerebral Aß plaque load in cortex, hippocampus and cerebellum were analyzed. RESULTS: Visual inspection and SUVs revealed an increased cerebral uptake of [18F]-florbetaben in APPswe/ PS1dE9 mice compared with wild type mice especially in the cortex, the hippocampus and the cerebellum. However, SUV ratios (SUVRs) relative to cerebellum revealed only significant differences in the hippocampus between the APPswe/PS1dE9 and wild type mice but not in cortex; this differential effect may reflect the lower plaque area in the cortex than in the hippocampus as found in the histological analysis. CONCLUSION: The findings suggest that histopathological characteristics of Aß plaque size and spatial distribution can be depicted in vivo using [18F]-florbetaben in the APPswe/PS1dE9 mouse model.

[Amyloid positron-emission-tomography with [18 F]-florbetaben in the diagnostic workup of dementia patients]. / Amyloid-Positronenemissionstomographie mit [18 F]-Florbetaben in der Demenzdiagnostik.

BACKGROUND: To this day the definite diagnosis of Alzheimer's disease still relies on post-mortem histopathological detection of neurofibrillary tangles and beta-amyloid deposits. Amyloid positron emission tomography (PET) is a new diagnostic tool that enables the in vivo quantification of pathological beta-amyloid deposits. The aim of the current study was to evaluate to what extent 18F-florbetaben-PET (FBB-PET) influences the diagnosis of patients with dementia. MATERIAL AND METHODS: Imaging with FBB-PET was performed on 33 patients from our outpatient department for cognitive neurology. Beforehand all patients underwent a comprehensive clinical, neuropsychiatric and laboratory examination as well as imaging by means of magnetic resonance imaging (MRI) and fluorodeoxyglucose-PET. The working diagnoses before and after FBB-PET imaging were compared. RESULTS: 17 out of 33 patients were scored as FBB-PET positive. In four cases the initial diagnosis had to be changed to Alzheimer's disease (three cases) and cerebral amyloid angiopathy (one case) due to the positive FBB-PET scan. 16 patients showed a negative FBB-PET scan. In three patients the initial diagnosis of Alzheimer's disease could be ruled out due to the negative FBB-PET scan. Overall, in 7 out of 33 examined patients the initial diagnosis had to be changed because of the findings of the FBB-PET scan. In 24 patients the initial diagnosis was confirmed by the results of the FBB-PET scan. CONCLUSION: Amyloid-PET is currently no standard procedure in the diagnosis of dementia; however, it can be a helpful additional diagnostic tool when used according to the "Appropriate Use Criteria" and the S3 guidelines on dementia in cases of unclear clinical presentation, atypically early age of onset as well as in patients with persistent or progressive unexplained mild cognitive impairment. By facilitating early diagnosis amyloid-PET imaging allows patient selection for therapeutic drug trials.

[A Pair of Siblings with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis and a Novel Thr462Lysfs Mutation in the TBK1 Gene]. / Ein Geschwisterpaar mit frontotemporaler Lobärdegeneration und amyotropher Lateralsklerose und einer neuen Mutation im TBK1-Gen (Thr462Lysfs).

We report on a pair of siblings with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) and a novel Thr462Lysfs mutation in the TANK-binding kinase 1 (TBK1) gene identified through the European Early-Onset Dementia Consortium. The patients presented at the age of 77 and 75 years and displayed dementia and bulbar symptoms as well as progressive paresis. After a progressive course, both of them died only a few months after diagnosis. Most recently, TBK1 mutations were identified in patients with FTD and ALS. A loss of expression of the mutant allele, leading to 50 % reduced TBK1 protein levels, seems to be causative. The occurrence of TBK1 mutations in FTD and ALS underlines the fact that FTD and ALS are part of the same disease spectrum. For future therapeutic trials, characterization of TBK1 mutation carriers in presymptomatic cohorts, such as the genetic frontotemporal dementia initiative (GENFI), is of great importance.

Metastatic mammary carcinoma despite histologically negative sentinel lymph nodes: are there any indicators for estimating recurrence and metastasis rates?.

OBJECTIVE: This study aimed to identify indicators for an increased frequency of recurrent or metastatic disease in women with mammary carcinoma staged negative for nodal involvement. MATERIALS AND METHODS: 202/270 patients (age: mean 57.5, range 24-83 years) with histologically confirmed early stage mammary carcinoma negative for metastasis to the sentinel lymph nodes (SLN) were observed with respect to their clinical course for a mean period of 3.6 years following SLN extirpation. RESULTS: Forty of 202 patients with negative SLN underwent chemotherapy (38/188 in the recurrence-free group vs. 2/14 in the group with progressive disease) and 79% of both subcollectives did not undergo chemotherapy. Seven of 188 of patients in the recurrence-free group received immunotherapy and none of the patients in the group with disease progression were treated with this modality. One hundred sixty-two of 202 patients with negative SLN underwent hormone therapy, 157/188 in the recurrence-free group and 5/14 in the group with disease progression. One hundred sixty-four of 202 patients with negative nodal status received adjuvant radiation therapy of the affected breast, 156/188 in the recurrence-free group and 8/14 in the group with disease progression. CONCLUSIONS: When assessing the risk profile for disease recurrence or the occurrence of metastatic disease, statistically significant differences with respect to disease progression were identified for the parameters chemo-, antibody, hormone, and radiation therapy. The preliminary observations of this study show that even those patients in an early disease stage and with negative SLNs profit from these adjuvant non-surgical therapy options.

[Microsurgical Autologous Lymph Vessel Transplantation: Does Harvesting Lymphatic Vessel Grafts Induce Lymphatic Transport Disturbances in the Donor Limb?]. / Mikrochirurgische autologe Lymphgefäß-Transplantation: Verursacht die Entnahme von Lymphgefäß-Transplantaten Lymphtransportstörungen an der Spenderextremität?

OBJECTIVE: The aim of this study was to determine whether the extirpation of lymphatic vessels induces lymphatic transport disturbances in the donor limb of patients following the harvest of lymph vessel grafts. PATIENTS, MATERIAL AND METHODS: A total of 19 consecutive patients (15 females, 4 males; mean age 51.5 years, range 21.8-72.3) were examined by lymphoscintigraphy before and after surgery. The patients had previously been diagnosed with upper or lower limb lymphoedema in accordance with the criteria of the International Society of Lymphology, and autologous lymph vessel transplantation had been intended for treatment. Since only patients with normal scintigraphic tests at the harvesting site were considered for treatment, all consecutive patients (n=19) had normal scintigraphic tests of the donor limb prior to surgery. In order to quantify the visual scintigraphic findings, a well established numeric transport index (TI) was used, which combined 5 visual parameters of transport kinetics. To that end, the following visually assessed criteria were evaluated: temporal and spatial kinetics, radiopharmaceutical distribution pattern, time to appearance of inguinal lymph nodes, qualitative visualisation of lymph nodes and lymph vessels. RESULTS: All patients underwent a preoperative scintigraphic baseline study and a postoperative scintigraphic follow-up after autologous lymphatic vessel grafting. The mean time period from the baseline study to the date of microsurgical lymph vessel transplantation was 3.5 months (median 2.5 months). The scintigraphic follow-up was performed 48.6 months (median 57.8 months) following transplantation. In all patients the postoperative TI was very close to the TI calculated in the preoperative baseline scintigraphy, and all TIs were within the normal range (TI<10). The absolute value of deviation of pre- vs. post-operative transport indices was calculated to be 0.2 on average (maximum 0.4). CONCLUSIONS: The results show that microsurgical transfer of lymph vessel grafts is possible without compromising lymphatic drainage of the donor limb if safety precautions are taken into account.

Chylothorax and chylous ascites. Clinical utility of planar scintigraphy and tomographic imaging with SPECT/CT.

UNLABELLED: The aim was to analyze conventional planar scintigraphy and SPECT/CT in patients clinically suspicious for chylothorax or chylous ascites. Lymphoscintigraphy was performed for two reasons: first, to help diagnose chylothorax or -abdomen, by demonstrating diffuse uptake in fluid accumulations, and then secondly, to detect the site of leakage to test the prediction that additional use of SPECT/CT-technique improves upon the diagnostic value of planar lymphoscintigraphy in the baseline detection of thoraco-abdominal lymphatic disorders. PATIENTS, MATERIAL, METHODS: From 7/2008-7/2014 a total of 24 consecutive patients (8 woman, 16 men; age, range 31-79 years) presenting with clinical symptoms suspicious for chylothorax and/or chylous ascites were examined by planar lymphoscintigraphy (n = 26) and additional tomographic SPECT/CT- (n = 22) or SPECT-technique (n = 2). RESULTS: Chylothorax could be scintigraphically confirmed in n = 9, chylous ascites in n = 5 scintigraphies, and excluded in n = 10 patients. In all planar scintigraphy findings of pathological lymph drainage regions (n = 14), SPECT/CT delivered additional relevant information, notably the anatomic localization of the lymphatic leakage. For the baseline detection of thoraco-abdominal lymphatic transport disorders, lymphoscintigraphy showed sensitivity of 88%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 80%. CONCLUSIONS: Our findings show that due to the particular advantages presented by tomographic separation of overlapping sources, SPECT/CT specifies better the anatomical sites, improving the localization of lymphatic leakage in aid of planning surgical re-interventions.

[A Pair of Siblings with a rare R5H-Mutation in Exon 1 of the MAPT-Gene]. / Ein Geschwisterpaar mit einer seltenen Tau-Gen-Mutation (MAPT R5H).

We report on a female patient presenting with primary progressive aphasia (PPA) and her brother presenting with psychosis. Both siblings had an R5H-mutation in exon 1 of the MAPT-gene. The PPA patient presented for the first time at the age of 72 years with a 4-year-history of language impairment. After a progressive course the patient died at the age of 76 years. The R5H-MAPT-gene mutation detected in the siblings has been described only once in 2002 by Hayashi et al. [1]. In this previous case from Japan, a 75-year-old patient initially displayed amnesia and disorientation. He became bedridden, with progressive mutism and rigidity of the upper extremities. Noteworthy are the manifold signs and symptoms in R5H-mutations and the late age of onset. For future trials, the detection of biomarkers for frontotemporal lobar degeneration in presymptomatic cohorts like the genetic frontotemporal dementia initiative (GENFI) is of help for stratifying subjects at risk.

Amyloid-PET predicts inhibition of de novo plaque formation upon chronic γ-secretase modulator treatment.

In a positron-emission tomography (PET) study with the ß-amyloid (Aß) tracer [(18)F]-florbetaben, we previously showed that Aß deposition in transgenic mice expressing Swedish mutant APP (APP-Swe) mice can be tracked in vivo. γ-Secretase modulators (GSMs) are promising therapeutic agents by reducing generation of the aggregation prone Aß42 species without blocking general γ-secretase activity. We now aimed to investigate the effects of a novel GSM [8-(4-Fluoro-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[1-(3-methyl-[1,2,4]thiadiazol-5-yl)-piperidin-4-yl]-amine (RO5506284) displaying high potency in vitro and in vivo on amyloid plaque burden and used longitudinal Aß-microPET to trace individual animals. Female transgenic (TG) APP-Swe mice aged 12 months (m) were assigned to vehicle (TG-VEH, n=12) and treatment groups (TG-GSM, n=12), which received daily RO5506284 (30 mg kg(-1)) treatment for 6 months. A total of 131 Aß-PET recordings were acquired at baseline (12 months), follow-up 1 (16 months) and follow-up 2 (18 months, termination scan), whereupon histological and biochemical analyses of Aß were performed. We analyzed the PET data as VOI-based cortical standard-uptake-value ratios (SUVR), using cerebellum as reference region. Individual plaque load assessed by PET remained nearly constant in the TG-GSM group during 6 months of RO5506284 treatment, whereas it increased progressively in the TG-VEH group. Baseline SUVR in TG-GSM mice correlated with Δ%-SUVR, indicating individual response prediction. Insoluble Aß42 was reduced by 56% in the TG-GSM versus the TG-VEH group relative to the individual baseline plaque load estimates. Furthermore, plaque size histograms showed differing distribution between groups of TG mice, with fewer small plaques in TG-GSM animals. Taken together, in the first Aß-PET study monitoring prolonged treatment with a potent GSM in an AD mouse model, we found clear attenuation of de novo amyloidogenesis. Moreover, longitudinal PET allows non-invasive assessment of individual plaque-load kinetics, thereby accommodating inter-animal variations.

Altered serotonin and dopamine transporter availabilities in brain of depressed patients upon treatment with escitalopram: A [123 I]ß-CIT SPECT study.

Altered SERT and DAT availabilities during treatment with escitalopram were investigated with [(123)I]2ß-carbomethoxy-3ß-(4-iodophenyl)tropane (ß-CIT) SPECT in a series of patients fulfilling the criteria for unipolar major depressive disorder (MDD). 27 patients (10m, 42±16y) with diagnosis of MDD were recruited for the study. All patients underwent neuropsychiatric testing for assessment of Hamilton Depression (HAM-D) and Beck Depression Inventory (BDI) scores. At baseline, [(123)I]ß-CIT SPECT recordings were acquired 4h (SERT-weighted) and 20-24h p.i (DAT-weighted). Follow-up scans and neuropsychiatric testing were performed after six weeks of stable escitalopram medication. Voxel-wise parametric maps of specific/ non-specific ratios-1 (~BPND) were calculated. At baseline, DAT-weighted BPND was 5.06±0.81 in striatum and SERT-weighted BPND was 0.94±0.18 in thalamus. There were significant negative correlations with age for DAT in striatum (R=-0.60; p<0.01) and SERT in thalamus (R=-0.45; p<0.05). Under SSRI treatment there was an apparent 42% occupancy of SERT in thalamus (p<0.0001), whereas DAT availability increased significantly by 20% in striatum (p<0.001); higher apparent SERT occupancy in thalamus was associated with lesser DAT increase in striatum (R=-0.62; p<0.005). The low apparent SERT occupancy may be confounded by alterations in SERT expression during treatment. Thus, [(123)I]ß-CIT SPECT revealed age-dependent declines in DAT and SERT availabilities in un-medicated MDD patients, comparable to that seen previously in healthy controls. At follow-up, the SSRI-evoked increase in DAT was less pronounced in the older patients, even though apparent SERT occupancy and clinical improvement were not age-dependent. Present findings may have implications for escitalopram dosage and side effect profile in younger MDD patients.

Magnetic resonance imaging versus lymphoscintigraphy for the assessment of focal lymphatic transport disorders of the lower limb: first experiences.

PURPOSE: To compare the diagnostic accuracy of magnetic resonance imaging (MR-lymphangiography) and lymphoscintigraphy for assessment of focal lesions of the peripheral lymphatic system. Patients with focal lymphatic transport disorders might benefit from surgi-cal interventions. PATIENTS, METHODS: We examined by lymphoscintigraphy and MR-lymphangiography a total of 85 lower limbs in 46 consecutive patients (33 women; mean age 41 years; range 9-79 years) presenting with uni- or bilateral lymphedema. MR-lymphangiographies were obtained at isotropic sub-millimeter resolution with a 3.0 Tesla magnet after injection of gadolinium contrast medium. MR-lymphangiography was reviewed by radiologists, whereas lymphoscintigraphy was reviewed by nuclear medicine physicians. The images were examined for localization and distribution of any focal lesions of the lymphatic vessel system. Diagnostic accuracy of the MR-approach was calculated relative to the lymphoscintigraphy gold standard. RESULTS: There was substantial correlation of results by the two modalities (κ = 0.62). MR-lymphangiography had sensitivity of 68%, specificity of 91%, positive predictive value of 82%, and negative predictive value of 83%. CONCLUSIONS: Imaging findings of both lymphoscintigraphy and MR-lymphangiography showed good diagnostic accuracy. MR-lymphangiography proved more information about anatomic location of focal lesions of the lymphatic vessels, but use of MR-lymphangiography is currently constrained due to the requirement for off-label subcutaneous injection of gadolinium chelates. Consequently, and due to its superior sensitivity lymphoscintigraphy remains the most common imaging method to assess functional lymphatic disorders of the lower limb.

[Hereditary diffuse leukencephalopathy with spheroids: a microgliopathy due to CSF1 receptor impairment]. / Hereditäre diffuse Leukenzephalopathie mit Sphäroiden : Eine Mikrogliopathie durch Fehlfunktion des CSF1-Rezeptors.

Hereditary diffuse leukencephalopathy with spheroids (HDLS) is a rare progressive form of leukodystrophy with variable clinical presentation and little known pathophysiology. Characteristic pathological features at brain biopsy or postmortem can support the diagnosis. The genetic basis of HDLS was elusive until 2011 when mutations in the colony-stimulating factor 1 receptor (CSF1R) gene were identified as the cause. Mutations in the CSF1R gene had previously been associated with tumor development, including hematological malignancies. We report three patients with HDLS who carried missense mutations in the CSF1R gene, two of them novel (p.L582P and p.V383L). Particularly in younger patients with rapid cognitive decline and/or leukencephalopathy of unknown origin, HDLS appears to be more common than previously thought. Various compounds acting on the CSF1 receptor are available from the treatment of hemato-oncological malignancies, so novel therapeutic approaches could be developed for this devastating condition.

[Radiological diagnostics in CUP syndrome]. / Radiologische Diagnostik des CUP-Syndroms.

CLINICAL/METHODICAL ISSUE: Imaging plays an essential role in the therapeutic management of cancer of unknown primary (CUP) patients for localizing the primary tumor, for the identification of tumor entities for which a dedicated therapy regimen is available and for the characterization of clinicopathological subentities that direct the subsequent diagnostic and therapeutic strategy. STANDARD RADIOLOGICAL METHODS: Modalities include conventional x-ray, computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound as well as positron emission tomography (PET)-CT and MRI-PET. PERFORMANCE: In whole body imaging CT has a high sensitivity for tumor entities which frequently present as a metastasized cancer illness. According to the current literature CT is diagnostic in 86% of patients with pancreatic carcinoma, in 36% of patients with colon carcinoma and in 74% of patients with lung carcinoma. Additionally a meta-analysis showed that for patients with squamous cell carcinoma and cervical lymph node metastases a positive diagnosis was possible in 22% of the cases using CT, in 36% using MRI and in 28-57% using 18F-fluorodeoxyglucose PET-CT ((18)F-FDG PET-CT). In addition, MRI plays an important role in the localization of primary occult tumors (e.g. breast and prostate) because of its high soft tissue contrast and options for functional imaging. ACHIEVEMENTS: At the beginning of the diagnostic algorithm stands the search for a possible primary tumor and CT of the neck, thorax and abdomen is most frequently used for whole body staging. Subsequent organ-specific imaging examinations follow, e.g. mammography in women with axillary lymphadenopathy. For histological and immunohistochemical characterization of tumor tissue, imaging is also applied to identify the most accessible and representative tumor manifestation for biopsy. Tumor biopsy may be guided by CT, MRI or ultrasound and MRI also plays a central role in the localization of primary occult tumors because of superior soft tissue contrast and options for functional imaging (perfusion, diffusion), e.g. investigation of breast carcinoma or prostate carcinoma. PRACTICAL RECOMMENDATIONS: Whole body staging stands at the beginning of the diagnostic algorithm in CUP syndrome to localize a potential primary tumor. Clinically, contrast-enhanced CT of the neck, thorax and abdomen is frequently applied; however, many studies have demonstrated augmented sensitivity of (18)F-FDG PET-CT for the detection of primary tumors and metastatic tumor manifestations.

Detection of underlying malignancy in patients with paraneoplastic neurological syndromes: comparison of 18F-FDG PET/CT and contrast-enhanced CT.

PURPOSE: To determine the value of combined (18)F-FDG PET/CT with diagnostic contrast-enhanced CT (CECT) in detecting primary malignancies and metastases in patients with paraneoplastic neurological syndromes (PNS) and to compare this with CECT alone. METHODS: PET/CT scans from 66 patients with PNS were retrospectively evaluated. Two blinded readers initially reviewed the CECT portion of each PET/CT scan. In a second session 3 months later, the readers analysed the combined PET/CT scans. Findings on each study were assessed using a four-point-scale (1 normal/benign; 2 inconclusive, further diagnostic work-up may be necessary; 3 malignant; 4 inflammatory). Sensitivity and specificity for malignant findings were calculated for PET/CT and CECT. Interreader agreement was determined by calculating Cohen's kappa. Pooled data from clinical follow-up (including histopathology and follow-up imaging, median follow-up 20.0 months) served as the reference gold standard. RESULTS: Both readers classified 12 findings in ten patients (15%) as malignant on the PET/CT scans (two patients had two primary tumours). One such imaging finding (suspected thymic cancer) was false-positive (i.e. benign histology). The most common tumours were bronchial carcinoma (n = 3), lymph node metastases of gynaecological tumours (n = 3) and tonsillar carcinoma (n = 2). Three of 12 findings (25%) were not detected by CECT alone (cervical carcinoma, lymph node metastasis and tonsillar carcinoma). In a per-patient analysis, sensitivity and specificity for malignant findings were 100% and 90% for PET/CT and 78% and 88% for CECT. In 24% (reader 1) and 21% (reader 2) of the patients, the PET/CT findings were inconclusive. Of these findings, 57% (reader 1) and 56% (reader 2) were only diagnosed with PET (e.g. focal FDG uptake of the thyroid, gastrointestinal tract and ovaries). On follow-up, none of these findings corresponded to malignancy. Overall agreement between the two readers was excellent with a Cohen's kappa of 0.95 ± 0.04 (p < 0.001) for PET/CT and 0.97 ± 0.03 (p < 0.001) for CECT alone. CONCLUSION: In this cohort of patients with PNS, PET/CT exhibited improved detection of underlying malignancy versus CECT alone. While hybrid imaging produces a greater number of inconclusive findings, sensitivity is increased for the detection of head and neck and gynaecological malignancies as well as metastatic lymph node involvement.