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Matrix metalloproteinases 9 (MMP9) are enzymes involved in regulating neuroplasticity in the hippocampus. This, combined with evidence for disrupted hippocampal structure and function in schizophrenia, has prompted our current investigation into the relationship between MMP9 and hippocampal volumes in schizophrenia. 34 healthy individuals (mean age = 32.50, male = 21, female = 13) and 30 subjects with schizophrenia (mean age = 33.07, male = 19, female = 11) underwent a blood draw and T1-weighted magnetic resonance imaging. The hippocampus was automatically segmented utilizing FreeSurfer. MMP9 plasma levels were measured with ELISA. ANCOVAs were conducted to compare MMP9 plasma levels (corrected for age and sex) and hippocampal volumes between groups (corrected for age, sex, total intracranial volume). Spearman correlations were utilized to investigate the relationship between symptoms, medication, duration of illness, number of episodes, and MMP9 plasma levels in patients. Last, we explored the correlation between MMP9 levels and hippocampal volumes in patients and healthy individuals separately. Patients displayed higher MMP9 plasma levels than healthy individuals (F(1, 60) = 21.19, p < 0.0001). MMP9 levels correlated with negative symptoms in patients (R = 0.39, p = 0.035), but not with medication, duration of illness, or the number of episodes. Further, patients had smaller left (F(1,59) = 9.12, p = 0.0040) and right (F(1,59) = 6.49, p = 0.013) hippocampal volumes. Finally, left (R = -0.39, p = 0.034) and right (R = -0.37, p = 0.046) hippocampal volumes correlated negatively with MMP9 plasma levels in patients. We observe higher MMP9 plasma levels in SCZ, associated with lower hippocampal volumes, suggesting involvement of MMP9 in the pathology of SCZ. Future studies are needed to investigate how MMP9 influences the pathology of SCZ over the lifespan, whether the observed associations are specific for schizophrenia, and if a therapeutic modulation of MMP9 promotes neuroprotective effects in SCZ.

Many methods applied to data acquired by various imaging modalities have been evaluated for their benefit in localizing lesions in magnetic resonance (MR) negative epilepsy patients. No approach has proven to be a stand‐alone method with sufficiently high sensitivity and specificity. The presented study addresses the potential benefit of the automated fusion of results of individual methods in presurgical evaluation. We collected electrophysiological, MR, and nuclear imaging data from 137 patients with pharmacoresistant MR‐negative/inconclusive focal epilepsy. A subgroup of 32 patients underwent surgical treatment with known postsurgical outcomes and histopathology. We employed a Gaussian mixture model to reveal several classes of gray matter tissue. Classes specific to epileptogenic tissue were identified and validated using the surgery subgroup divided into two disjoint sets. We evaluated the classification accuracy of the proposed method at a voxel‐wise level and assessed the effect of individual methods. The training of the classifier resulted in six classes of gray matter tissue. We found a subset of two classes specific to tissue located in resected areas. The average classification accuracy (i.e., the probability of correct classification) was significantly higher than the level of chance in the training group (0.73) and even better in the validation surgery subgroup (0.82). Nuclear imaging, diffusion‐weighted imaging, and source localization of interictal epileptic discharges were the strongest methods for classification accuracy. We showed that the automatic fusion of results can identify brain areas that show epileptogenic gray matter tissue features. The method might enhance the presurgical evaluations of MR‐negative epilepsy patients., There is no known stand‐alone imaging method for epileptogenic zone identification in nonlesional epilepsy. We examined the potential benefit of the automated fusion of results from individual methods. The proposed method can identify epileptogenic tissue with high accuracy at the voxel level, that is, at a millimeters scale.

This first-ever study demonstrates the applicability of a fiber Bragg grating (FBG) system for MR cardiac triggering of cardiovascular magnetic resonance at 3 Tesla. The unique patented system senses body movements caused by cardiac activity using a non-invasive ballistocardiography (BCG) sensor. The pilot research compares a novel FBG-based system with clinically used triggering systems based on electrocardiography (ECG) and pulse oximetry (POX). The pilot pre-clinical study was conducted on 8 subjects at a Siemens Prisma 3T MR Scanner. The study compares images from two basic cardiac sequences, TRUE FISP (Free Induction Decay Steady-State Precession) and PSIR (Phase Sensitive Inversion Recovery), using objective methods and subjective evaluation by clinical experts. The study presents original results that confirm the applicability of optical sensors in the field of cardiac triggering having a number of advantages in comparison to conventional solutions, such as no eddy current interference, ease of placement of the sensor on the patient's body, and senor reusability. The proposed FBG-based system achieves comparable results with the most frequently used and most accurate ECG-based and POX-based clinical systems. In terms of subjective evaluation by experts, the FBG system outperformed the POX-based system used in clinical practice. Web of Science 8 181223 181205

Background: The research of primary progressive multiple sclerosis (PPMS) has not been able to capitalize on recent progresses in advanced magnetic resonance imaging (MRI) protocols.Objective: The presented cross-sectional study evaluated the utility of four different MRI relaxation metrics and diffusion-weighted imaging in PPMS.Methods: Conventional free precession T1 and T2, and rotating frame adiabatic T1ρ and T2ρ in combination with diffusion-weighted parameters were acquired in 13 PPMS patients and 13 age- and sex-matched controls.Results: T1ρ, a marker of crucial relevance for PPMS due to its sensitivity to neuronal loss, revealed large-scale changes in mesiotemporal structures, the sensorimotor cortex, and the cingulate, in combination with diffuse alterations in the white matter and cerebellum. T2ρ, particularly sensitive to local tissue background gradients and thus an indicator of iron accumulation, concurred with similar topography of damage, but of lower extent. Moreover, these adiabatic protocols outperformed both conventional T1 and T2 maps and diffusion tensor/kurtosis approaches, methods previously used in the MRI research of PPMS.Conclusion: This study introduces adiabatic T1ρ and T2ρ as elegant markers confirming large-scale cortical gray matter, cerebellar, and white matter alterations in PPMS invisible to other in vivo biomarkers.

The effectivity of diffusion-weighted MRI methods in detecting the epileptogenic zone (EZ) was tested. Patients with refractory epilepsy (N=25) who subsequently underwent resective surgery were recruited. First, the extent of white matter (WM) asymmetry from mean kurtosis (MK) was calculated in order to detect the lobe with the strongest impairment. Second, a newly developed metric was used, reflecting a selection of brain areas with concurrently increased mean Diffusivity, reduced fractional Anisotropy, and reduced mean Kurtosis (iDrArK). A two-step EZ detection was performed as (1) lobe-specific detection, (2) iDrArK voxel-wise detection (with a possible lobe-specific restriction if the result of the first step was significant in a given subject). The method results were compared with the surgery resection zones. From the whole cohort (N=25), the numbers of patients with significant results were: 10 patients in lobe detection and 9 patients in EZ detection. From these subsets of patients with significant results, the impaired lobe was successfully detected with 100% accuracy; the EZ was successfully detected with 89% accuracy. The detection of the EZ using iDrArK was substantially more successful when compared with solo diffusional parameters (or their pairwise combinations). For a subgroup with significant results from step one (N=10), iDrArK without lobe restriction achieved 37.5% accuracy; lobe-restricted iDrArK achieved 100% accuracy. The study shows the plausibility of MK for detecting widespread WM changes and the benefit of combining different diffusional voxel-wise parameters.

This study describes a pilot clinical validation of a new low-cost system for the continuous monitoring of the human body's cardiorespiratory activities within the magnetic resonance examination area. This study primarily focuses on monitoring cardiac activity and the related cardiac triggering. The patented system tested by the authors is based on seismocardiography (SCG). The study was conducted on 18 subjects on a Siemens Prisma 3T MR scanner. Standard anatomical and diffusion sequences were used to test cardiac activity monitoring. A wide range of commonly used diagnostic sequences were used to test imaging of the heart by means of cardiac triggering. System functionality was verified against a commercially available electrocardiography (ECG) system. Monitoring of cardiac activity (detection of the R-R interval in ECG and the AO-AO interval in SCG) was objectively evaluated by determining the overall probability of correct detection (ACC), sensitivity (SE), positive predictive value (PPV), and harmonic mean between SE and PPV, i.e. F1. Imaging quality control using Cardiac Triggering was performed by subjective evaluation of images by the physicians. The study conducted clearly confirmed the functionality of the system in terms of continuous cardiac activity monitoring. In all 18 subjects, a mean PPV > 99% was achieved; F1 > 99 %; SE > 99 %; ACC > 98 %; 1.96 sigma < 3.5 bpm. Also, Cardiac Triggering functionality was confirmed by the physicians on the basis of analyzing cardiac images using the T1/T2 balanced echo sequences and the T1 flash sequence measured natively. Web of Science 7 118629 118608

This publication describes an original simple low-cost MR fully-compatible and safe fiber-optic breathing sensor (FOBS), which can be used for respiratory triggering and for monitoring the development of respiratory rate within the MR environment and can, thus, serve as prevention from the hyperventilation syndrome. The sensor is created by encapsulation of the Bragg grating into conventional nasal oxygen cannulas. The sensor is immune to minor patient movements, thus limiting movement artifacts to a minimum. Thanks to this fact it can be used for the retrospective/prospective respiratory gating. The sensor is immune to electromagnetic interference (EMI) and can thus be used in any magnetic field (1.5T, 3T, and 7T). The sensor prototype has been tested in both laboratory and real magnetic resonance (3T) environments relative to conventional pneumatic respiration references (PRR). The data measured were statistically evaluated using the objective Bland-Altman method (BAM) and the functionality of the proposed solution was confirmed. Respiratory Triggering functionality was confirmed by the radiologic doctors on the basis of analyzing images using the most used respiratory triggered T2 TSE 3D sequences and by objective method using the Blind/Referenceless Image Spatial Quality Evaluator (BRISQUE). Web of Science 7 123025 123013

Diffusion magnetic resonance imaging (dMRI) proved promising in patients with non-myelopathic degenerative cervical cord compression (NMDCCC), i.e., without clinically manifested myelopathy. Aim of the study is to present a fast multi-shell HARDI-ZOOMit dMRI protocol and validate its usability to detect microstructural myelopathy in NMDCCC patients. In 7 young healthy volunteers, 13 age-comparable healthy controls, 18 patients with mild NMDCCC and 15 patients with severe NMDCCC, the protocol provided higher signal-to-noise ratio, enhanced visualization of white/gray matter structures in microstructural maps, improved dMRI metric reproducibility, preserved sensitivity (SE = 87.88%) and increased specificity (SP = 92.31%) of control-patient group differences when compared to DTI-RESOLVE protocol (SE = 87.88%, SP = 76.92%). Of the 56 tested microstructural parameters, HARDI-ZOOMit yielded significant patient-control differences in 19 parameters, whereas in DTI-RESOLVE data, differences were observed in 10 parameters, with mostly lower robustness. Novel marker the white-gray matter diffusivity gradient demonstrated the highest separation. HARDI-ZOOMit protocol detected larger number of crossing fibers (5–15% of voxels) with physiologically plausible orientations than DTI-RESOLVE protocol (0–8% of voxels). Crossings were detected in areas of dorsal horns and anterior white commissure. HARDI-ZOOMit protocol proved to be a sensitive and practical tool for clinical quantitative spinal cord imaging.

Differential diagnosis of the most common tremor syndromes – essential tremor (ET) and Parkinson's disease (PD) is burdened with high error rate. However, diagnostic MRI biomarkers applicable in this clinically highly relevant scenario remain an unfulfilled objective. The presented study was designed in search for possible candidate MRI protocols relevant for differential diagnostic process in tremor syndromes.10 non-advanced tremor-dominant PD patients meeting diagnostic criteria for clinically established PD, 12 isolated ET patients and 16 healthy controls were enrolled into this study. The study focused on relaxation MRI protocols – T1, T2, adiabatic T1ρ and adiabatic T2ρ due to their relatively low post-processing requirements enabling implementation into routine clinical practice. Compared to ET, PD patients had significantly longer T2 relaxation times in striata with dominant findings in the putamen contralateral to the clinically more affected body side. This difference was driven by alterations in the PD group as confirmed in the complementary comparison with healthy controls. According to the receiver operating characteristic analysis, this region provided a reasonable sensitivity of 0.91 and specificity of 0.89 in the differential diagnosis of PD and ET. In PD patients, we further found prolonged T1ρ in the substantia nigra compared to ET and healthy controls, and shorter T2 and T2ρ in the cerebellum compared to healthy controls. T2 relaxation time in the putamen contralateral to the clinically more affected body side is a plausible candidate diagnostic marker for the differentiation of PD and ET.

While previous studies suggested that perfusion abnormalities in Parkinson's disease (PD) are driven by dementia, our study aimed to identify perfusion underpinning of cognitive alteration in non-demented PD patients. Cerebral blood flow was measured using arterial spin labelling (ASL) in 28 PD patients (age 65 years ± 9.9 SD) and 16 age-matched healthy controls (HC) (age 65 years ± 7.8 SD), who also underwent neurological and cognitive testing. The 3D pseudocontinuous ASL and T2-weighted scans from 22 PD patients and 16 HC were analysed in a voxel-wise manner using SPM8 software. Associations between the ASL values in volumes of interest (VOIs) and behavioural and cognitive measures were assessed by Spearman correlation analysis. Posterior cortical hypoperfusion was found in PD patients compared to HC in the left supramarginal gyrus/superior temporal gyrus (VOI1) and left posterior cingulate/precuneus (VOI2). Positive correlation was revealed between perfusion in the VOI2 and Addenbrooke's Cognitive Examination Revised (ACE-R) scores after filtering out the effect of age, levodopa equivalent dose (LED), and total intracranial volume (TIV) (R = 0.51, p = 0.04). Conversely, negative correlation between VOI1 and ACE-R was detected (R = -0.62, p = 0.01) after regressing out the effects of motor impairment, age, LED, and TIV. In non-demented subjects with PD, blood flow abnormalities in precuneus/posterior cingulate were linked to the level of motor impairment and global cognitive performance. Oppositely, perfusion abnormalities in supramarginal gyrus might serve as a compensatory mechanism for brain degeneration and decreased cognitive performance.

Background Schizophrenia (SCZ) is a severe and chronic brain disorder that affects about 1% of the world population. It is among the most burdensome illnesses with a serious impact on patients, their families and society. To this day, a lot remains unknown about the neuropathological cause and etiology of SCZ. The prominent two-hit theory postulates that early neurodevelopmental abnormalities interact with a later “second hit” which occurs around symptom onset. Recent research points towards the role of inflammation in pathophysiology of schizophrenia. Matrix metalloproteinase-9 (MMP-9) was recently suggested as a potential key player in both first and second “hit” in the pathology of SCZ. It is considered to not only regulate brain development and synaptic plasticity, but to also mediate neuroinflammation. A point of interest for interaction with neuroinflammatory pathways is the Choroid Plexus (ChP). MMP-9 has been reported to be upregulated in ChP in SCZ. Since ChP regulates CSF production and permeability of the blood-CSF-barrier, MMP-9 upregulation in ChP might lead to its enlargement, as well as enlargement of the lateral ventricles and increased extracellular water volume, all found previously in SCZ. We investigate, for the first time, the relationship between MMP-9 blood plasma concentration and volume of ChP in patients with SCZ compared to healthy controls (HC). Methods We included 66 subjects (25 female = 38%, 41 male = 62%, mean age 32.59 +/- 9.14 years); 32 were patients with SCZ, 34 were HC. ELISA analysis was performed to measure MMP-9 blood concentrations in patients and HC. A whole brain, high-resolution three-dimensional T1-weighted magnetization prepared rapid gradient echo (MPRAGE) sequence scan was used to collect 240 sagittal slices, field of view = 224 x 224 mm2, 1 mm3 isotropic voxel, TR = 2.3 s, TE = 2.33 ms, flip angle = 8° on a 3T Siemens Magnetom Prisma. Structural T1 images underwent visual quality control, were realigned and parcellated into 176 gray and white matter regions using FreeSurfer software. Preliminary analyses were conducted comparing 1) MMP-9 levels between groups and 2) relating MMP-9 levels to ChP volume utilizing regression analyses. Results Patients with SCZ showed a strong upregulation of MMP-9 compared to HC (patients: 120 ± 60 ng/ml; HC: 60 ± 40 ng/ml; p < 0.0001). Furthermore, linear regression analyses - corrected for age and sex - demonstrated a positive association between concentration of MMP-9 and ChP volumes (left: R2 = .095, p < .01; right: R2 = .084, p < .02). Discussion To our knowledge, our study is the first to present preliminary evidence of an association between brain structure and MMP-9 peripheral upregulation in SCZ. Advanced evaluation of MMP-9 might enhance our understanding of illness cause, enable outcome predictions and paint the way for more individualized psychopharmacotherapy, as MMP-9 might serve as potential pharmacological target. However, further analyses are needed to validate our findings using as neuroanatomically precise methods as possible and to develop MMP-9 biomarkers that would capture central, as opposed to peripheral levels of MMP-9.

Diffusion Magnetic Resonance Imaging (dMRI) is a widely-utilized method for assessment of microstructural properties in the central nervous system i.e., the brain and spinal cord (SC). In the SC, almost all previous human studies utilized Diffusion Tensor Imaging (DTI), which cannot accurately model areas where white matter (WM) pathways cross or diverge. While High Angular Diffusion Resolution Imaging (HARDI) can overcome some of these limitations, longer acquisition times critically limit its applicability to clinical human studies. In addition, previous human HARDI studies have used limited spatial resolution, with typically a few slices and voxel size ~1 × 1 × 5 mm3 being acquired in tens of minutes. Thus, we have optimized a novel fast HARDI protocol that allows collecting dMRI data at high angular and spatial resolutions in clinically-feasible time. Our data was acquired, using a 3T Siemens Prisma scanner, in less than 9 min. It has a total of 75 diffusion-weighted volumes and high spatial resolution of 0.67 × 0.67 × 3 mm3 (after interpolation in Fourier space) covering the cervical segments C4–C6. Our preliminary results demonstrate applicability of our technique in healthy individuals with good correspondence between low fractional anisotropy (FA) gray matter areas from the dMRI scans, and the same regions delineated on T2-weighted MR images with spatial resolution of 0.35 × 0.35 × 2.5 mm3. Our data also allows the detection of crossing fibers that were previously shown in vivo only in animal studies.

INTRODUCTION While progressive MRI brain changes characterize advanced Parkinson's disease (PD), little has been discovered about structural alterations in the earliest phase of the disease, i.e. in patients with motor symptoms and with normal cognition. Our study aimed to detect grey matter (GM) and white matter (WM) changes in PD patients without cognitive impairment. METHODS Twenty PD patients and twenty-one healthy controls (HC) were tested for attention, executive function, working memory, and visuospatial and language domains. High-resolution T1-weighted and 60 directional diffusion-weighted 3T MRI images were acquired. The cortical, deep GM and WM volumes and density, as well as the diffusion properties of WM, were calculated. Analyses were repeated on data flipped to the side of the disease origin. RESULTS PD patients did not show any significant differences from HC in cognitive functioning or in brain volumes. Decreased GM intensity was found in the left superior parietal lobe in the right (p