Paradigm-shift: radiological changes in the asymptomatic iNPH-patient to be: an observational study.

BACKGROUND: Many radiological signs are known for the diagnosis of idiopathic normal pressure hydrocephalus (iNPH). However, there is little information about these signs in the pre-symptomatic phase. For pathophysiological investigative purposes we conducted a descriptive image analysis study on pre-symptomatic patients. METHODS: Patients that had contact with either the neurological or neurosurgical department of the university hospital Tuebingen from 2010 through 2016 with magnetic resonance images > 3 years before onset of symptoms, were included. The date of onset and severity of symptoms, date of first imaging and birth date were recorded. Evan's index (EI), width of the third ventricle (3VW), tight high convexity (THC), Sylvian fissure, extent of white matter hyperintensities and aqueductal flow were assessed in images before and around symptom onset. RESULTS: Ten patients were included. In all ten patients the first symptom was gait disturbance. Nine of ten pre-symptomatic images showed classic signs for iNPH. EI showed a significant increase between the pre-symptomatic and symptomatic phase. 3VW showed a trend for increase without significance. THC changed back and forth over time within some patients. CONCLUSIONS: In accordance with the scarce literature available, radiological changes are present at least 3 years before onset of iNPH-symptoms. EI seems to be a robust measure for pre-symptomatic radiological changes. Extrapolating the data, the development of iNPH typical changes might be an insidious process and the development of THC might be a variable and non-linear process. Further studies with larger sample sizes are necessary to put these findings into the pathophysiological perspective for the development of iNPH.

In vivo assessment of tumor heterogeneity in WHO 2016 glioma grades using diffusion kurtosis imaging: Diagnostic performance and improvement of feasibility in routine clinical practice.

PURPOSE: To assess the diagnostic performance of normalized and non-normalized diffusion kurtosis imaging (DKI) metrics extracted from different tumor volume data for grading glioma according to the integrated approach of the revised 2016 WHO classification. MATERIALS AND METHODS: Sixty patients with histopathologically confirmed glioma, who provided written informed consent, were retrospectively assessed between 01/2013 and 08/2016 from a prospective trial approved by the local institutional review board. Mean kurtosis (MK) and mean diffusivity (MD) metrics from DKI were assessed by two blinded physicians from four different volumes of interest (VOI): whole solid tumor including (VOItu-ed) and excluding perifocal edema (VOItu), infiltrative zone (VOIed), and single slice of solid tumor core (VOIslice). Intra-class correlation coefficient (ICC) was calculated to assess inter-rater agreement. One-way ANOVA was used to compare MK between 2016 CNS WHO tumor grades. Friedman's test compared MK and MD of each VOI. Spearman's correlation coefficient was used to correlate MK with 2016 CNS WHO tumor grades. ROC analysis was performed on MK for significant results. RESULTS: The MK assessment showed excellent inter-rater agreement for each VOI (ICC, 0.906-0.955). MK was significantly lower in IDHmutant astrocytoma (0.40±0.07), than in 1p/19q-confirmed oligodendroglioma (0.54±0.10, P=0.001) or IDHwild-type glioblastoma (0.68±0.13, P<0.001). MK and 2016 WHO tumor grades were strongly and positively correlated (VOItu-ed, r=0.684; VOItu, r=0.734; VOIed, r=0.625; VOIslice, r=0.698; P<0.001). CONCLUSIONS: Non-normalized MK values obtained from VOItu and VOIslice showed the best reproducibility and highest diagnostic performance for stratifying glioma according to the integrated approach of the recent 2016 WHO classification.

Combined PET/MRI: Global Warming-Summary Report of the 6th International Workshop on PET/MRI, March 27-29, 2017, Tübingen, Germany.

The 6th annual meeting to address key issues in positron emission tomography (PET)/magnetic resonance imaging (MRI) was held again in Tübingen, Germany, from March 27 to 29, 2017. Over three days of invited plenary lectures, round table discussions and dialogue board deliberations, participants critically assessed the current state of PET/MRI, both clinically and as a research tool, and attempted to chart future directions. The meeting addressed the use of PET/MRI and workflows in oncology, neurosciences, infection, inflammation and chronic pain syndromes, as well as deeper discussions about how best to characterise the tumour microenvironment, optimise the complementary information available from PET and MRI, and how advanced data mining and bioinformatics, as well as information from liquid biomarkers (circulating tumour cells and nucleic acids) and pathology, can be integrated to give a more complete characterisation of disease phenotype. Some issues that have dominated previous meetings, such as the accuracy of MR-based attenuation correction (AC) of the PET scan, were finally put to rest as having been adequately addressed for the majority of clinical situations. Likewise, the ability to standardise PET systems for use in multicentre trials was confirmed, thus removing a perceived barrier to larger clinical imaging trials. The meeting openly questioned whether PET/MRI should, in all cases, be used as a whole-body imaging modality or whether in many circumstances it would best be employed to give an in-depth study of previously identified disease in a single organ or region. The meeting concluded that there is still much work to be done in the integration of data from different fields and in developing a common language for all stakeholders involved. In addition, the participants advocated joint training and education for individuals who engage in routine PET/MRI. It was agreed that PET/MRI can enhance our understanding of normal and disrupted biology, and we are in a position to describe the in vivo nature of disease processes, metabolism, evolution of cancer and the monitoring of response to pharmacological interventions and therapies. As such, PET/MRI is a key to advancing medicine and patient care.

Assessment of metastatic colorectal cancer with hybrid imaging: comparison of reading performance using different combinations of anatomical and functional imaging techniques in PET/MRI and PET/CT in a short case series.

PURPOSE: The purpose was to investigate the diagnostic performance of different combinations of anatomical and functional imaging techniques in PET/MRI and PET/CT for the evaluation of metastatic colorectal cancer lesions. METHODS: Image data of 15 colorectal cancer patients (FDG-PET/CT and subsequent FDG-PET/MRI) were retrospectively evaluated by two readers in five reading sessions: MRI (morphology) alone, MRI/diffusion-weighted MRI (DWI), MRI/PET, MRI/DWI/PET; and PET/CT. Diagnostic performance of lesion detection with each combination was assessed in general and organ-based. The reference standard was given by histology and/or follow-up imaging. Separate analysis of mucinous tumours was performed. RESULTS: One hundred and eighty lesions (110 malignant) were evaluated (intestine n = 6, liver n = 37, lymph nodes n = 55, lung n = 4, and peritoneal n = 74). The overall lesion-based diagnostic accuracy was 0.46 for MRI, 0.47 for MRI/DWI, 0.57 for MRI/PET, 0.69 for MRI/DWI/PET and 0.66 for PET/CT. In the organ-based assessment, MRI/DWI/PET showed the highest accuracy for liver metastases (0.74), a comparable accuracy to PET/CT in peritoneal lesions (0.55), and in lymph node metastases (0.84). The accuracy in mucinous tumour lesions was limited in all modalities (MRI/DWI/PET = 0.52). CONCLUSIONS: PET/MRI including DWI is comparable to PET/CT in the evaluation of colorectal cancer metastases, with a markedly higher accuracy when using combined imaging data than the modalities separately. Further improvement is needed in the imaging of peritoneal carcinomatosis and mucinous tumours.

Staging of neuroendocrine tumours: comparison of [68Ga]DOTATOC multiphase PET/CT and whole-body MRI.

PURPOSE: In patients with a neuroendocrine tumour (NET), the extent of disease strongly influences the outcome and multidisciplinary therapeutic management. Thus, systematic analysis of the diagnostic performance of the existing staging modalities is necessary. The aim of this study was to compare the diagnostic performance of 2 whole-body imaging modalities, [(68)Ga]DOTATOC positron emission tomography (PET)/computed tomography (CT) and magnetic resonance imaging (MRI) in patients with NET with regard to possible impact on treatment decisions. MATERIALS AND METHODS: [(68)Ga]DOTATOC-PET/CT and whole-body magnetic resonance imaging (wbMRI) were performed on 51 patients (25 females, 26 males, mean age 57 years) with histologically proven NET and suspicion of metastatic spread within a mean interval of 2.4 days (range 0-28 days). PET/CT was performed after intravenous administration of 150 MBq [(68)Ga]DOTATOC. The CT protocol comprised multiphase contrast-enhanced imaging. The MRI protocol consisted of standard sequences before and after intravenous contrast administration at 1.5 T. Each modality (PET, CT, PET/CT, wbMRI) was evaluated independently by 2 experienced readers. Consensus decision based on correlation of all imaging data, histologic and surgical findings and clinical follow-up was established as the standard of reference. Lesion-based and patient-based analysis was performed. Detection rates and accuracy were compared using the McNemar test. P values <0.05 were considered significant. The impact of whole-body imaging on the treatment decision was evaluated by the interdisciplinary tumour board of our institution. RESULTS: 593 metastatic lesions were detected in 41 of 51 (80%) patients with NET (lung 54, liver 266, bone 131, lymph node 99, other 43). One hundred and twenty PET-negative lesions were detected by CT or MRI. Of all 593 lesions detected, PET identified 381 (64%) true-positive lesions, CT 482 (81%), PET/CT 545 (92%) and wbMRI 540 (91%). Comparison of lesion-based detection rates between PET/CT and wbMRI revealed significantly higher sensitivity of PET/CT for metastatic lymph nodes (100% vs 73%; P < 0.0001) and pulmonary lesions (100% vs 87%; P = 0.0233), whereas wbMRI had significantly higher detection rates for liver (99% vs 92%; P < 0.0001) and bone lesions (96% vs 82%; P < 0.0001). Of all 593 lesions, 22 were found only in PET, 11 only in CT and 47 only in wbMRI. The patient-based overall assessment of the metastatic status of the patient showed comparable sensitivity of PET/CT and MRI with slightly higher accuracy of PET/CT. Patient-based analysis of metastatic organ involvement revealed significantly higher accuracy of PET/CT for bone and lymph node metastases (100% vs 88%; P = 0.0412 and 98% vs 78%; P = 0.0044) and for the overall comparison (99% vs 89%; P < 0.0001). The imaging results influenced the treatment decision in 30 patients (59%) with comparable information from PET/CT and wbMRI in 30 patients, additional relevant information from PET/CT in 16 patients and from wbMRI in 7 patients. CONCLUSION: PET/CT and wbMRI showed comparable overall lesion-based detection rates for metastatic involvement in NET but significantly differed in organ-based detection rates with superiority of PET/CT for lymph node and pulmonary lesions and of wbMRI for liver and bone metastases. Patient-based analysis revealed superiority of PET/CT for NET staging. Individual treatment strategies benefit from complementary information from PET/CT and MRI.

Ovulation-selective genes: the generation and characterization of an ovulatory-selective cDNA library.

Ovulation-selective/specific genes, that is, genes preferentially or exclusively expressed during the ovulatory process, have been the subject of growing interest. We report herein studies on the use of suppression subtractive hybridization (SSH) to construct a 'forward' ovulation-selective/specific cDNA library. In toto, 485 clones were sequenced and analyzed for homology to known genes with the basic local alignment tool (BLAST). Of those, 252 were determined to be nonredundant. Of these 252 nonredundant clones, 98 were analyzed by probing mouse preovulatory and postovulatory ovarian cDNA. Twenty-five clones (26%) failed to show any signal, and 43 cDNAs tested thus far display a true ovulation-selective/specific expression pattern. In this communication, we focus on one such ovulation-selective gene, the fatty acid elongase 1 (FAE-1) homolog, found to be localized to the inner periantral granulosa and to the cumulus granulosa cells of antral follicles. The FAE-1 gene is a beta-ketoacyl-CoA synthase belonging to the fatty acid elongase (ELO) family, which catalyzes the initial step of very long-chain fatty acid synthesis. All in all, the present study accomplished systematic identification of those hormonally regulated genes that are expressed in the ovary in an ovulation-selective/specific manner. These ovulation-selective/specific genes may have significant implications for the understanding of ovarian function in molecular terms and for the development of innovative strategies for both the promotion of fertility and its control.