Value of T2 Mapping MRI for Prostate Cancer Detection and Classification.

Currently, multi-parametric prostate MRI (mpMRI) consists of a qualitative T <sub>2</sub> , diffusion weighted, and dynamic contrast enhanced imaging. Quantification of T <sub>2</sub> imaging might further standardize PCa detection and support artificial intelligence solutions. To evaluate the value of T <sub>2</sub> mapping to detect prostate cancer (PCa) and to differentiate PCa aggressiveness. Retrospective single center cohort study. Forty-four consecutive patients (mean age 67 years; median PSA 7.9 ng/mL) with mpMRI and verified PCa by subsequent targeted plus systematic MR/ultrasound (US)-fusion biopsy from February 2019 to December 2019. Standardized mpMRI at 3 T with an additionally acquired T <sub>2</sub> mapping sequence. Primary endpoint was the analysis of quantitative T <sub>2</sub> values and contrast differences/ratios (CD/CR) between PCa and benign tissue. Secondary objectives were the correlation between T <sub>2</sub> values, ISUP grade, apparent diffusion coefficient (ADC) value, and PI-RADS, and the evaluation of thresholds for differentiating PCa and clinically significant PCa (csPCa). Mann-Whitney test, Spearman's rank (r <sub>s</sub> ) correlation, receiver operating curves, Youden's index (J), and AUC were performed. Statistical significance was defined as P < 0.05. Median quantitative T <sub>2</sub> values were significantly lower for PCa in PZ (85 msec) and PCa in TZ (75 msec) compared to benign PZ (141 msec) or TZ (97 msec) (P < 0.001). CD/CR between PCa and benign PZ (51.2/1.77), respectively TZ (19.8/1.29), differed significantly (P < 0.001). The best T <sub>2</sub> -mapping threshold for PCa/csPCa detection was for TZ 81/86 msec (J = 0.929/1.0), and for PZ 110 msec (J = 0.834/0.905). Quantitative T <sub>2</sub> values of PCa did not correlate significantly with the ISUP grade (r <sub>s</sub> = 0.186; P = 0.226), ADC value (r <sub>s</sub> = 0.138; P = 0.372), or PI-RADS (r <sub>s</sub> = 0.132; P = 0.392). Quantitative T <sub>2</sub> values could differentiate PCa in TZ and PZ and might support standardization of mpMRI of the prostate. Different thresholds seem to apply for PZ and TZ lesions. However, in the present study quantitative T <sub>2</sub> values were not able to indicate PCa aggressiveness. 2 TECHNICAL EFFICACY: Stage 2

Big GABA II: Water-referenced edited MR spectroscopy at 25 research sites

Accurate and reliable quantification of brain metabolites measured in vivo using 1H magnetic resonance spectroscopy (MRS) is a topic of continued interest. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, spectrally edited γ-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T1-weighted structural images were acquired and segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels

Ketamine effects on brain function - simultaneous fMRI/EEG during a visual oddball task

Behavioral and electrophysiological human ketamine models of schizophrenia are used for testing compounds that target the glutamatergic system. However, corresponding functional neuroimaging models are difficult to reconcile with functional imaging and electrophysiological findings in schizophrenia. Resolving the discrepancies between different observational levels is critical to understand the complex pharmacological ketamine action and its usefulness for modeling schizophrenia pathophysiology.We conducted a within-subject, randomized, placebo-controlled pharmacoimaging study in twenty-four male volunteers. Subjects were given low-dose S-ketamine (bolus prior to functional imaging: 0.1mg/kg during 5min, thereafter continuous infusion: 0.015625mg/kg/min reduced by 10% every ten minutes) or placebo while performing a visual oddball task during simultaneous functional magnetic resonance imaging (fMRI) with continuous recording of event-related potentials (P300) and electrodermal activity (EDA). Before and after intervention, psychopathological status was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Altered State of Consciousness (5D-ASC) Rating Scale.P300 amplitude and corresponding BOLD responses were diminished in the ketamine condition in cortical regions being involved in sensory processing/selective attention. In both measurement modalities separation of drug conditions was achieved with area under the curve (AUC) values of up to 0.8-0.9. Ketamine effects were also observed in the clinical, behavioral and peripheral physiological domains (Positive and Negative Syndrome Scale, reaction hit and false alarm rate, electrodermal activity and heart rate) which were in part related to the P300/fMRI measures.The findings from our ketamine experiment are consistent across modalities and directly related to observations in schizophrenia supporting the validity of the model. Our investigation provides the first prototypic example of a pharmacoimaging study using simultaneously acquired fMRI/EEG

Hybrid (18)F-FDG PET-MRI of the hand in rheumatoid arthritis: initial results

18F-fluorodeoxyglucose PET (18F-FDG PET) is highly sensitive to inflammatory changes within the synovial tissue in rheumatoid arthritis (RA). However, the highest spatial resolution for soft tissue can be achieved with MRI. Here, we report on the first true hybrid PET-MRI examination of the hand in early RA exploiting the advantages of both modalities. PET-MRI was performed with a prototype of an APD-based magneto-insensitive BrainPET detector (Siemens Healthcare, Erlangen, Germany) operated within a standard 3T MR scanner (MAGNETOM Trio, Siemens). PET images were normalized, random, attenuation and scatter-corrected, iteratively reconstructed and calibrated to yield standardized uptake values (SUV) of 18F-FDG uptake. T1-weighted TSE in coronal as well as sagittal orientation prior to and following Gadolinium administration were acquired. Increased 18F-FDG uptake was present in synovitis and tenovaginitis as identified on contrast-enhanced MRI. The tracer distribution was surrounding the metacarpophalangeal joints II and III. Maximum SUV of 3.1 was noted. In RA, true hybrid 18F-FDG PET-MRI of the hand is technically feasible and bears the potential to directly visualize inflammation

A novel MRI-biomarker candidate for Alzheimer's disease composed of regional brain volume and perfusion variables

Background: Earlier evidence indicates that regional cerebral volume (rVOL) and blood flow (rCBF) variables carry independent information on incipient and early Alzheimer's disease (AD) and combining these modalities may increase discriminant performance. We compared single variables and combinations regarding their power for optimizing diagnostic accuracy. Methods: Twelve cognitively normal elderly controls (CN), 30 subjects with mild cognitive impairment (MCI) and 15 with mild AD were examined by structural and perfusion-weighted magnetic resonance imaging (MRI) in single sessions at 1.5 Tesla. rVOLs were measured by manual volumetry, and rCBFs were calculated with a ROI-based co-localization technique. Results: Applying single MRI variables for the differentiation of AD versus CN, the area under curve (AUC) of receiver operating characteristic curves (ROCCs) was highest for rVOL variables (maximum of 0.972 for right amygdala). A composite marker selected and weighted by logistic regression containing left amygdalar rCBF, left hippocampal and right amygdalar rVOLs gave a diagnostic accuracy for AD versus CN of 100%. Internal cross-validation revealed a reliability of 88.9%. Conclusions: Whilst external revalidation is mandatory employing a naturalistic sample containing disease controls, our phase I/II findings demonstrate that deducing composite markers from multimodal MRI acquisitions can optimize diagnostic accuracy for AD

The relation of regional cerebral perfusion and atrophy in mild cognitive impairment (MCI) and early Alzheimer's dementia

The spatial and temporal relations between regional cerebral blood flow (rCBF) and brain volume (rVOL) changes in incipient and early Alzheimer's dementia (AD) are not fully understood. The participants comprised 30 subjects with mild cognitive impairment (MCI) and 15 with mild AD who were examined using structural and perfusion-weighted magnetic resonance imaging (MRI) at 1.5 Tesla. Hippocampus and amygdala volumes were measured by manual volumetry. A region-of-interest co-localisation method was used to calculate rCBF values. DNA samples were genotyped for apolipoprotein E (APO E). In comparisons of AD with MCI, rCBF was reduced in the posterior cingulum only, while profound rVOL reductions occurred in both right and left amygdala and in the right hippocampus, and as a trend, in the left hippocampus. Brain volumes of the hippocampus and the amygdala were uncorrelated with the respective rCBF variables in both MCI and AD. Hippocampal but not amygdalar volumes were associated with presence of one or two APOE epsilon4 alleles in MCI and mild AD, while there was no association of APOE epsilon4 allele with rCBF. These data support earlier indications that rCBF and rVOL changes are at least partly dissociated in the early pathogenesis of AD and heterogeneously associated with the APOE risk allele. The data also support the concept of functional compensatory brain activation and the diaschisis hypothesis as relevant in incipient and early AD

Big GABA: Edited MR spectroscopy at 24 research sites

Magnetic resonance spectroscopy (MRS) is the only biomedical imaging method that can noninvasively detect endogenous signals from the neurotransmitter γ-aminobutyric acid (GABA) in the human brain. Its increasing popularity has been aided by improvements in scanner hardware and acquisition methodology, as well as by broader access to pulse sequences that can selectively detect GABA, in particular J-difference spectral editing sequences. Nevertheless, implementations of GABA-edited MRS remain diverse across research sites, making comparisons between studies challenging. This large-scale multi-vendor, multi-site study seeks to better understand the factors that impact measurement outcomes of GABA-edited MRS. An international consortium of 24 research sites was formed. Data from 272 healthy adults were acquired on scanners from the three major MRI vendors and analyzed using the Gannet processing pipeline. MRS data were acquired in the medial parietal lobe with standard GABA+ and macromolecule- (MM-) suppressed GABA editing. The coefficient of variation across the entire cohort was 12% for GABA + measurements and 28% for MM-suppressed GABA measurements. A multilevel analysis revealed that most of the variance (72%) in the GABA + data was accounted for by differences between participants within-site, while site-level differences accounted for comparatively more variance (20%) than vendor-level differences (8%). For MM-suppressed GABA data, the variance was distributed equally between site- (50%) and participant-level (50%) differences. The findings show that GABA + measurements exhibit strong agreement when implemented with a standard protocol. There is, however, increased variability for MM-suppressed GABA measurements that is attributed in part to differences in site-to-site data acquisition. This study's protocol establishes a framework for future methodological standardization of GABA-edited MRS, while the results provide valuable benchmarks for the MRS community