Inversion Recovery Magnetic Resonance Imaging Research Articles

Changes in leukoencephalopathy and serum neurofilament after (neo)adjuvant chemotherapy for breast cancer

BackgroundPrevious case studies have provided evidence for chemotherapy-induced leukoencephalopathy in patients with breast cancer. However, prospective research is lacking. Hence, we investigated leukoencephalopathy before and after chemotherapy and its association with a serum neuroaxonal damage marker. MethodsThis prospective cohort study included 40 patients receiving chemotherapy for breast cancer, and two age- and education-matched control groups, recruited between 2018 and 2021 (31–64 years of age). The latter control groups consisted of 39 chemotherapy-naïve patients and 40 healthy women. Fluid-attenuated inversion-recovery magnetic resonance imaging was used for lesion volumetry (total, juxtacortical, periventricular, infratentorial, and deep white matter) and blood serum to measure neurofilament light chain (NfL) levels. Acquisition took place pre-chemotherapy and three months and one-year post-chemotherapy, or at corresponding intervals. Within/between group differences were compared using robust mixed-effects modeling, and associations between total lesion volume and serum-NfL with linear regression. ResultsStronger increases in deep white matter lesion volumes were observed shortly post-chemotherapy, compared with healthy women (ßstandardized=0.09, pFDR<0.001). Increases in total lesion volume could mainly be attributed to enlargement of existing lesions (mean±SD, 0.12±0.16 mL), rather than development of new lesions (0.02±0.02 mL). A stronger increase in serum-NfL concentration was observed shortly post-chemotherapy compared with both control groups (ß>0.70, p<0.004), neither of which showed any changes over time, whereas a decrease was observed compared with healthy women one-year post-chemotherapy (ß=-0.54, p = 0.002). Serum-NfL concentrations were associated with lesion volume one-year post-chemotherapy (or at matched timepoint; ß=0.36, p = 0.010), whereas baseline or short-term post-therapy levels or changes were not. ConclusionThese results underscore the possibility of chemotherapy-induced leukoencephalopathy months post-treatment, as well as the added value of serum-NfL as a prognostic marker for peripheral/central neurotoxicity. Translational relevancePrevious case studies have provided evidence of chemotherapy-induced leukoencephalopathy in patients with breast cancer. However, prospective studies to estimate longitudinal changes are currently missing. In this study, we used longitudinal fluid-attenuated inversion-recovery magnetic resonance imaging to assess white matter lesion volumes in patients treated for non-metastatic breast cancer and healthy women. Our findings demonstrate that chemotherapy-treated patients exhibit stronger increases in lesion volumes compared with healthy women, specifically in deep white matter, at three months post-chemotherapy. Increases could mainly be attributed to enlargement of existing lesions, rather than development of new lesions. Last, serum concentrations of neurofilament light chain, a neuroaxonal damage marker, increased shortly after chemotherapy and long-term post-chemotherapy levels were associated with lesion volumes. These findings highlight the potential of this non-invasive serum marker as a prognostic marker for peripheral and/or central neurotoxicity. Implementation in clinical practice could aid in therapeutic decisions, assessing disease activity, or monitoring treatment response.

Segmenting white matter hyperintensities in brain magnetic resonance images using convolution neural networks

White matter hyperintensities (WMHs) are found on magnetic resonance (MR) images of older individuals and are associated with many neurodegenerative disorders, although the exactrole of WMHs in Alzheimer’s disease and other dementias remains an open area of research. Fluid-attenuated inversion recovery (FLAIR) MR imaging sequences show WMHs with good image contrast. Manual segmentation of WMHs on FLAIR images is the widely accepted “gold standard”, however, this step is often time-consuming and has a high inter-rater variability. The absence of an automated, robust and accurate approach to segment WMHs remains a processing bottleneck. We explored convolutional neural networks (CNNs) for performing semantic segmentation of WMHs in FLAIR images. Two sets of experiments were conducted: (1) Variations of U-shaped CNNs (U-Nets) were evaluated in 186 individuals, specifically, four architectures (VGG16, VGG19, ResNet152 and EfficientNetB0) having three dimensionalities (2D, 2.5D and 3D). (2) New data from 60 individuals were added to test the generalizability of U-Net, LinkNet and Feature-Pyramid Network (FPN) variants. The first experiment showed that the 2.5D implementation with VGG16 or VGG19 was the most suitable configuration when segmenting WMH (F-measure > 95% and intersection-over-union > 90%). The second experiment confirmed generalizability of these variants when using unprocessed FLAIR images.

The value of postcontrast delayed 3D fluid-attenuated inversion recovery MRI in the diagnosis of unilateral peripheral vestibular dysfunction.

Clinically, unilateral peripheral vestibular dysfunction (UPVD) with dizziness or vertigo as the chief complaint is quite common. This study aimed to investigate the correlations between 3-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D-FLAIR MRI) findings and cochleovestibular function test results in patients with UPVD and to explore the possible etiologies of UPVD. This retrospective study enrolled 76 patients with UPVD. Endolymphatic hydrops (EH) and perilymphatic enhancement (PE) in the vestibule and cochlea on 3D-FLAIR images, their correlations with the parameters of the cochleovestibular function test and vascular risk factors, and the immunological findings of patients with EH and PE were assessed. Of the included patients, 48.7% showed positive MRI findings (the presence of EH and PE on 1 side). The pure-tone average (PTA) was higher in patients with cochlear PE than in those with vestibular (P=0.014) and cochlear EH (P=0.02). The canal paresis (CP) value was also higher in patients with vestibular PE than in those with vestibular (P=0.002) and cochlear EH (P=0.003). Video head impulse test (vHIT) gains were lower in patients with vestibular and cochlear PE than in those with vestibular and cochlear EH (P<0.001). A positive correlation was observed between the degree of vestibular and cochlear EH and PTA (both P values <0.001). PTA and CP with a cutoff value of 32 dB and 46.5%, respectively, yielded high sensitivity and specificity in determining positive MRI findings (P<0.001 and P=0.029, respectively). The prevalence of vascular risk factors was significantly higher in patients with PE than in those with EH (P=0.033). (I) Nearly half of the patients UPVD exhibited abnormal MRI findings. Cutoff values for PTA and CP of 32 dB and 46.5%, respectively, indicated that patients were more likely to have abnormal imaging findings. (II) The severity of EH was positively correlated with hearing impairment. (III) Patients with PE showed severe hearing impairment and vestibular dysfunction, which was presumed to be associated with vascular damage.

Magnetic properties of iron-filled hydrogel clusters: a model system for quantitative susceptibility mapping with MRI

Quantitative approaches in clinical Magnetic Resonance Imaging (MRI) benefit from the availability of adequate phantoms. Ideally, the phantom material should reflect the complexity of signals encountered in vivo. In the present study we validate and characterize clusters consisting of sodium-polyacrylate embedded in an alginate matrix that are unloaded or loaded with iron for Quantitative Susceptibility Mapping (QSM), yielding a non-uniform iron distribution and tissue-mimicking MRI properties. Vibrating sample magnetometry (VSM) was used to characterize the phantom material and verify the accuracy of previous MRI-based observations of the QSM-based molar susceptibility (χM). MRI at 14.1 T with high resolution acquisitions was used to determine the size of hydrogel clusters and to further investigate the suitability of the phantom material as a model system for QSM at high field. VSM demonstrated that the iron-solution used for manufacturing the phantoms consisted of ferric iron. The χM of clusters with a constant iron-to-polyacrylate-ratio (8.3 μg/mg) observed with VSM was 50.7 ± 8.0 ppb mM−1 but showed a tendency towards saturation at total iron concentrations &amp;gt;1 mM. On unwrapped and background corrected phase-images obtained with gradient-echo MRI and an isotropic voxel size of 37 μm at 14.1T, the iron-free clusters had a roundish shape and blurry border with an equivalent sphere diameter of 276 ± 230 µm and a QSM of 7 ± 7 ppb. Iron-loading led to strong phase wrapping, necessitating the use of short echo times, or short inter-echo delays below 10 ms at 14.1 T. The equivalent sphere diameter of the iron-loaded clusters was estimated to 400–500 µm as verified using different MRI modalities (spin-echo, inversion recovery, and gradient echo MRI). With a constant iron-to-polyacrylate ratio, the cluster density was 10 mm−3 mM−1 iron. In agreement with previous observations, χM of samples with a constant amount of polyacrylate was 50.6 ± 11.4 ppb mM−1 at 3 T while samples containing clusters with a constant iron-to-polyacrylate-ratio yielded χM = 56.1 ± 6.3 ppb mM−1 at 3T and 55.6 ± 0.7 ppb mM−1 at 14.1 T. In conclusion we found that the molar susceptibility of the proposed model system corresponds to that predicted for ferritin in vivo loaded with 3000 iron atoms. The reproducibility was within 12% across MR scanners, batches, and phantom types and compared well with results obtained with vibrating sample magnetometry.

An imaging‑based diagnostic approach to vascular anomalies of the oral and maxillofacial region.

The accurate diagnosis of vascular anomalies (VAs) is considered a challenging endeavor. Misdiagnosis of VAs can lead clinicians in the wrong direction, such as the performance of an unnecessary biopsy or inappropriate surgical procedures, which can potentially lead to unforeseen consequences and increase the risk of patient injury. The purpose of the present study was to develop an approach for the diagnosis of VAs of the oral and maxillofacial region based on computed tomography (CT), magnetic resonance imaging (MRI) and dynamic contrast-enhanced MRI (DCE-MRI). In the present study, the CT and MR images of 87 VAs were examined, and the following imaging features were evaluated: Detectability of the lesion, the periphery of the lesion, the inner nature of the lesion, the density of the lesion on CT, the signal intensity of the lesion on MRI, the detectability of phleboliths and the shape of the lesion. A total of 29 lesions were further evaluated using the contrast index (CI) curves created from the DCE-MRI images. A diagnostic diagram, which is based on the imaging features of VAs and CI curve patterns, was subsequently extrapolated. The results obtained demonstrated that the VAs were detected more readily by MRI compared with CT, whereas the detectability of phleboliths was superior when using CT compared with MRI. VAs showed a propensity for homogeneous isodensity on CT, whereas, by contrast, they exhibited a propensity for heterogeneous hyperdensity on CE-CT. VAs also showed a propensity for homogeneous intermediate signal intensity when performing T1-weighted imaging (T1WI), heterogeneous high signal intensity when performing short tau inversion recovery MRI, and heterogeneous high signal intensity when performing fat-saturated CE-T1WI. The CI curves of VAs were found to exhibit a specific pattern: Of the 29 CI curves, 23 (79.3%) showed early weak enhancement, followed by a plateau leading up to 400-600 sec. An imaging-based diagnostic diagram was ultimately formulated. This diagram can act as an aid for radiologists when they are expecting to find a VA, and hopefully serve the purpose of simplifying the diagnostic process. Taken together, the findings of the present study indicated that DCE-MRI may be considered a useful tool for the diagnosis of VAs.

Diagnostic performance of double inversion recovery MRI sequence for synovitis of the wrist joints in rheumatoid arthritis.

To assess the diagnostic accuracy of double inversion recovery (DIR) magnetic resonance imaging (MRI) sequences for synovitis of the wrist joints in patients with rheumatoid arthritis (RA). Participants with newly diagnosed RA were enrolled between November 2019 and November 2020. MRI examinations of the wrist joints were performed using a contrast-enhanced T1-weighted imaging sequence (CE-T1WI) and DIR sequence. We measured synovitis score, number of synovial areas, synovial volume, mean synovium-to-bone signal ratio (SBR), and synovial contrast-to-noise ratio (SNR). The inter-reviewer agreement rated on a four-point scale was evaluated by calculating the weighted k statistics. Two MRI sequences were assessed using Bland-Altman analyses, and the diagnostic performance of DIR images was calculated using the chi-square test. A total of 47 participants were evaluated, and 282 joint regions in 5076 images were reviewed by two readers. There was no significant difference in synovitis scores (P = 0.67), number of synovial areas (P = 0.89), and synovial volume (P = 0.086) between the two MRI sequences. DIR images showed better SBR and SNR (all P < 0.01). There was good agreement between the two reviewers in terms of synovitis distribution (κ = 0.79). The synovitis was well agreed upon by the two readers according to Bland-Altman analyses. Using CE-T1WI as the reference standard, DIR imaging demonstrated a sensitivity of 94.1% and a specificity of 84.6% at the patient level. The non-contrast DIR sequence showed good consistency with CE-T1WI and potential for evaluating synovitis in patients with RA.

Noninvasive investigations of human glymphatic dynamics in a diseased model.

To explore human glymphatic dynamics in a diseased model via a noninvasive technique. Patients with reversible vasoconstriction syndrome (RCVS) presenting with blood-brain barrier disruption, i.e., para-arterial gadolinium leakage on 3-T 3-dimensional isotropic contrast-enhanced T2-fluid-attenuated inversion recovery (CE-T2-FLAIR) magnetic resonance imaging (MRI), were prospectively enrolled. Consecutive 9-min-CE-T2-FLAIR for 5-6 times (early panel) after intravenous gadolinium-based contrast agent (GBCA) administration and one time-varying deferred scan of noncontrast T2-FLAIR (delayed panel) were performed. In Bundle 1, we measured the calibrated signal intensities (cSIs) of 10 different anatomical locations. In Bundle 2, brain-wide measurements of para-arterial glymphatic volumes, means, and medians of the signal intensities were conducted. We defined mean (mCoIs) or median (mnCoIs) concentration indices as products of volumes and signal intensities. Eleven subjects were analyzed. The cSIs demonstrated early increase (9min) in perineural spaces: (cranial nerve [CN] V, p = 0.008; CN VII + VII, p = 0.003), choroid plexus (p = 0.003), white matter (p = 0.004) and parasagittal dura (p = 0.004). The volumes, mCoIs, and mnCoIs demonstrated increasing rates of enhancement after 9 to 18min and decreasing rates after 45 to 54min. The GBCA was transported centrifugally and completely removed within 961-1086min after administration. The exogenous GBCA leaked into the para-arterial glymphatics could be completely cleared around 961 to 1086min after administration in a human model of BBB disruption. The tracer enhancement started variously in different intracranial regions but was eventually cleared centrifugally to brain convexity, probably towards glymphatic-meningeal lymphatics exits. Glymphatic clearance time intervals and the centrifugal directions assessed by a noninvasive approach may have implications for clinical glymphatic evaluation in the near future. • This study aimed to investigate the human glymphatic dynamics in a noninvasive diseased model. • The intracranial MR-detectable gadolinium-based contrast agents were removed centrifugally within 961 to 1086min. • The glymphatic dynamics was demonstrable by enhancing MRI in an in vivo diseased model noninvasively.

White matter hyperintensities associated with impulse control disorders in Parkinson’s Disease

Impulse control disorders (ICDs) in Parkinson's disease (PD) are increasingly recognized as clinically significant non-motor features that potentially impair the quality of life. White matter hyperintensities (WMHs), detected by magnetic resonance imaging, are frequently observed in PD and can be associated with both motor- and certain non-motor symptoms. Given the limited number of non-motor features studied in this context, our aim was to reveal the potential association between the severity of WMHs and ICDs in PD. Fluid-attenuated inversion recovery magnetic resonance images were retrospectively evaluated in 70 patients with PD (48 males; 59.3 ± 10.1 years). The severity of WMHs was assessed by Fazekas scores and by the volume and number of supratentorial WMHs. ICDs were evaluated using the modified Minnesota Impulsive Disorders Interview. Significant interaction between age and the severity of WMHs was present for ICDs. In our younger patients (< 60.5 years), severity of WMHs was positively associated with ICDs (p = 0.004, p = 0.021, p < 0.001 and p < 0.001, respectively for periventricular white matter and total Fazekas scores and the volume and number of WMHs). Our study supports the hypothesis that WMHs of presumed vascular origin may contribute to ICDs in PD. Future prospective studies are needed to assess the prognostic relevance of this finding.

Prevalence of Venous Infarction in Patients With Cerebral Venous Thrombosis: Baseline Diffusion-Weighted MRI and Follow-Up MRI.

A venous pattern of infarction on neuroimaging is used as a clue to undiagnosed cerebral venous thrombosis (CVT); prevention of venous infarction is a goal of CVT management; and venous infarction is a factor used for clinical prognostication. Despite widespread use of the term venous infarct, the prevalence of true venous infarction is unclear. Our primary aim was to determine the prevalence of venous infarction in patients with CVT. We also measured the prevalence of diffusion abnormality without infarction, vasogenic edema, and intracranial hemorrhage. Single-center, retrospective cohort study using a registry of 110 consecutive patients admitted to hospital with cerebral venous thrombosis between 2004 and 2014. Inclusion criteria were brain magnetic resonance imaging (MRI) and contrast-enhanced venography at presentation, and repeat brain MRI ≥1 month later. Exclusion criteria were dural arteriovenous fistula, arteriovenous malformation, cavernous sinus thrombosis, or previous neurosurgical procedure. Main outcome was proportion of patients with venous infarction (irreversible ischemic injury) diagnosed using diffusion-weighted MRI at presentation, confirmed using T2-weighted fluid-attenuated inversion recovery MRI ≥1 month later, and reported with 95% CI using the Wilson score interval method. We also report the prevalence of transient diffusion MRI abnormality without infarction, vasogenic edema, and intracranial hemorrhage. Seventy-three patients met the inclusion criteria, and after exclusions, the final study population was 59 patients with median age 41 years (interquartile range, 32-57). Venous infarction occurred in 12% (7/59 [95% CI, 6%-23%]) of patients, and final infarct volume was >1 mL in only 5.1% (3/59) of patients. An additional 8% (5/59 [95% CI, 4%-18%]) of patients had a transient diffusion MRI abnormality without infarction. Prevalence of cerebral vasogenic edema and intracranial hemorrhage were 66% (39/59 [95% CI, 53%-77%]) and 54% (32/59 [95% CI, 41%-66%]), respectively. In patients with CVT, venous infarction is uncommon and venous infarcts are typically very small. Vasogenic edema and hemorrhage are more common consequences of CVT.

Tau influences the severity of delusions in older persons with early‐stage cognitive decline

AbstractBackgroundThe relationship between delusional severity and structural brain changes in patients with cognitive decline is unclear. In prior work by our group, we conducted texture and volume analysis of Normal Appearing Brain Matter (NABM) using FLAIR MRI sequences in a cognitively impaired delusional cohort. Our results demonstrated that with more severe delusions, greater global brain disease burden and tissue degeneration in NABM is apparent. In this study we examined the relationship between our findings and neurodegenerative biomarkers, ApoE4 and plasma tau.MethodsA total of 42 patients with Alzhiemer’s disease (AD) or Mild Cognitive Impairment (MCI) with delusions as identified by the Neuropsychiatric Inventory‐Quick version (NPI‐Q) were selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). From fluid‐attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) images, Brain extraction and intensity standardization alghorthims were applied to extract the normal‐appearing brain matter (NABM). Three biomarkers were measured from the NABM region, which included volume and two texture features called integrity and damage that measure the structural integrity of tissue and tissue damage. Statistical analysis included a multivariable stepwise regression of each biomarker as a dependent variable across delusional severity groups 1 (lowest severity) to 3 (highest severity) and the inclusion of sex, age, education, ApoE4 and plasma tau as co‐variates.ResultsData were gathered on the 42 participants representing 164 MRI scans. Significant associations were found between baseline plasma tau, delusional severity group 3 for the NABM integrity and volume biomarkers (p&lt;.05). Additionally, ApoE4 homozygotes were signficantly associated to NABM volume, integrity and damage, though no association was found with delusional severity.ConclusionThese findings suggest that plasma tau may be linked to both delusional severity and structural alterations within the NABM while ApoE4 status is more strongly associated with structural alterations in the NABM with no effect on delusional severity. Further longitudinal studies are required to establish plasma tau associated mechanisms of delusional severity.

Spatial patterns of white matter hyperintensities: a systematic review.

White matter hyperintensities are an important marker of cerebral small vessel disease. This disease burden is commonly described as hyperintense areas in the cerebral white matter, as seen on T2-weighted fluid attenuated inversion recovery magnetic resonance imaging data. Studies have demonstrated associations with various cognitive impairments, neurological diseases, and neuropathologies, as well as clinical and risk factors, such as age, sex, and hypertension. Due to their heterogeneous appearance in location and size, studies have started to investigate spatial distributions and patterns, beyond summarizing this cerebrovascular disease burden in a single metric-its volume. Here, we review the evidence of association of white matter hyperintensity spatial patterns with its risk factors and clinical diagnoses. We performed a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement. We used the standards for reporting vascular changes on neuroimaging criteria to construct a search string for literature search on PubMed. Studies written in English from the earliest records available until January 31st, 2023, were eligible for inclusion if they reported on spatial patterns of white matter hyperintensities of presumed vascular origin. A total of 380 studies were identified by the initial literature search, of which 41 studies satisfied the inclusion criteria. These studies included cohorts based on mild cognitive impairment (15/41), Alzheimer's disease (14/41), Dementia (5/41), Parkinson's disease (3/41), and subjective cognitive decline (2/41). Additionally, 6 of 41 studies investigated cognitively normal, older cohorts, two of which were population-based, or other clinical findings such as acute ischemic stroke or reduced cardiac output. Cohorts ranged from 32 to 882 patients/participants [median cohort size 191.5 and 51.6% female (range: 17.9-81.3%)]. The studies included in this review have identified spatial heterogeneity of WMHs with various impairments, diseases, and pathologies as well as with sex and (cerebro)vascular risk factors. The results show that studying white matter hyperintensities on a more granular level might give a deeper understanding of the underlying neuropathology and their effects. This motivates further studies examining the spatial patterns of white matter hyperintensities.

A Fully Automated Visual Grading System for White Matter Hyperintensities of T2-Fluid Attenuated Inversion Recovery Magnetic Resonance Imaging.

The Fazekas scale is one of the most commonly used visual grading systems for white matter hyperintensity (WMH) for brain disorders like dementia from T2-fluid attenuated inversion recovery magnetic resonance (MR) images (T2-FLAIRs). However, the visual grading of the Fazekas scale suffers from low-intra and inter-rater reliability and high labor-intensive work. Therefore, we developed a fully automated visual grading system using quantifiable measurements. Our approach involves four stages: (1) the deep learning-based segmentation of ventricles and WMH lesions, (2) the categorization into periventricular white matter hyperintensity (PWMH) and deep white matter hyperintensity (DWMH), (3) the WMH diameter measurement, and (4) automated scoring, following the quantifiable method modified for Fazekas grading. We compared the performances of our method and that of the modified Fazekas scale graded by three neuroradiologists for 404 subjects with T2-FLAIR utilized from a clinical site in Korea. The Krippendorff's alpha across our method and raters (A) versus those only between the radiologists (R) were comparable, showing substantial (0.694 vs. 0.732; 0.658 vs. 0.671) and moderate (0.579 vs. 0.586) level of agreements for the modified Fazekas, the DWMH, and the PWMH scales, respectively. Also, the average of areas under the receiver operating characteristic curve between the radiologists (0.80 ± 0.09) and the radiologists against our approach (0.80 ± 0.03) was comparable. Our fully automated visual grading system for WMH demonstrated comparable performance to the radiologists, which we believe has the potential to assist the radiologist in clinical findings with unbiased and consistent scoring.

Young versus older subject diffusion magnetic resonance imaging data for virtual white matter lesion tractography.

White matter hyperintensity (WMH) lesions on T2 fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) and changes in adjacent normal-appearing white matter can disrupt computerized tract reconstruction and result in inaccurate measures of structural brain connectivity. The virtual lesion approach provides an alternative strategy for estimating structural connectivity changes due to WMH. To assess the impact of using young versus older subject diffusion MRI data for virtual lesion tractography, we leveraged recently available diffusion MRI data from the Human Connectome Project (HCP) Lifespan database. Neuroimaging data from 50 healthy young (39.2 ± 1.6 years) and 46 healthy older (74.2 ± 2.5 years) subjects were obtained from the publicly available HCP-Aging database. Three WMH masks with low, moderate, and high lesion burdens were extracted from the WMH lesion frequency map of locally acquired FLAIR MRI data. Deterministic tractography was conducted to extract streamlines in 21 WM bundles with and without the WMH masks as regions of avoidance in both young and older cohorts. For intact tractography without virtual lesion masks, 7 out of 21 WM pathways showed a significantly lower number of streamlines in older subjects compared to young subjects. A decrease in streamline count with higher native lesion burden was found in corpus callosum, corticostriatal tract, and fornix pathways. Comparable percentages of affected streamlines were obtained in young and older groups with virtual lesion tractography using the three WMH lesion masks of increasing severity. We conclude that using normative diffusion MRI data from young subjects for virtual lesion tractography of WMH is, in most cases, preferable to using age-matched normative data.

Histopathological correlations and fat replacement imaging patterns in recessive limb-girdle muscular dystrophy type 12.

Despite the widespread use of proton density fat fraction (PDFF) measurements with magnetic resonance imaging (MRI) to track disease progression in muscle disorders, it is still unclear how these findings relate to histopathological changes in muscle biopsies of patients with limb-girdle muscular dystrophy autosomal recessive type 12 (LGMDR12). Furthermore, although it is known that LGMDR12 leads to a selective muscle involvement distinct from other muscular dystrophies, the spatial distribution of fat replacement within these muscles is unknown. We included 27 adult patients with LGMDR12 and 27 age-matched and sex-matched healthy controls and acquired 6-point Dixon images of the thighs and T1 and short tau inversion recovery (STIR) MR images of the whole body. In 16 patients and 15 controls, we performed three muscle biopsies, one in the semimembranosus, vastus lateralis, and rectus femoris muscles, which are severely, intermediately, and mildly affected in LGMDR12, respectively. We correlated the PDFF to the fat percentage measured on biopsies of the corresponding muscles, as well as to the Rochester histopathology grading scale. In patients, we demonstrated a strong correlation of PDFF on MRI and muscle biopsy fat percentage for the semimembranosus (r=0.85, P<0.001) and vastus lateralis (r=0.68, P=0.005). We found similar results for the correlation between PDFF and the Rochester histopathology grading scale. Out of the five patients with inflammatory changes on muscle biopsy, three showed STIR hyperintensities in the corresponding muscle on MRI. By modelling the PDFF on MRI for 18 thigh muscles from origin to insertion, we observed a significantly inhomogeneous proximo-distal distribution of fat replacement in all thigh muscles of patients with LGMDR12 (P<0.001), and different patterns of fat replacement within each of the muscles. We showed a strong correlation of fat fraction on MRI and fat percentage on muscle biopsy for diseased muscles and validated the use of Dixon fat fraction imaging as an outcome measure in LGMDR12. The inhomogeneous fat replacement within thigh muscles on imaging underlines the risk of analysing only samples of muscles instead of the entire muscles, which has important implications for clinical trials.

Suppression of inner ear signal intensity on fluid-attenuated inversion recovery magnetic resonance imaging in cats with vestibular disease.

Otitis media/interna (OMI) is the most common cause of peripheral vestibular disease in cats. The inner ear contains endolymph and perilymph, with perilymph being very similar in composition to cerebrospinal fluid (CSF). As a very-low-protein fluid, it would be expected that normal perilymph should suppress on fluid-attenuated inversion recovery (FLAIR) MRI sequences. Based on this, we hypothesized that MRI FLAIR sequences should provide a non-invasive way of diagnosing inflammatory/infectious diseases such as OMI in cats, something that has previously been demonstrated in humans and, more recently, in dogs. This was a retrospective cohort study in which 41 cats met the inclusion criteria. They were placed into one of four groups, based on presenting complaint: clinical OMI (group A); inflammatory central nervous system (CNS) disease (group B); non-inflammatory structural disease (group C); and normal brain MRI (control group; group D). Transverse T2-weighted and FLAIR MRI sequences at the level of the inner ears bilaterally were compared in each group. The inner ear was selected as a region of interest using Horos, with a FLAIR suppression ratio calculated to account for variability in signal intensity between MRIs. This FLAIR suppression ratio was then compared between groups. Statistical analyses were performed by an experienced statistician, with a general linear model used to compare mean FLAIR suppression ratio, CSF nucleated cell count and CSF protein concentration between groups. The OMI group (group A) had significantly lower FLAIR suppression scores compared with all other groups. The CSF cell count was also significantly increased in the OMI (group A) and inflammatory CNS disease (group B) groups compared with the control group (group D). This study demonstrates the utility of MRI FLAIR sequences in diagnosing presumptive OMI in cats, similarly to in humans and dogs. This study is relevant to practicing veterinary neurologists and radiologists in interpreting MRI findings in cats with suspected OMI.

White matter hyperintensities had a correlation with the cerebral perfusion level, but no correlation with the severity of large vessel stenosis in the anterior circulation.

The contribution of large vessel stenosis to the development of white matter hyperintensities (WMHs) has not been fully elucidated. This study aims to explore the correlation between ipsilateral white matter hyperintensities (WMHs) and the severity of large vessel stenosis in the anterior circulation and cerebral perfusion level, as well as analyze the factors influencing WMHs. A cross-sectional study of 150 patients with unilateral anterior circulation large vessel stenosis of ≥50% was conducted. The severity of ipsilateral WMHs was assessed by Fazekas scale on T2-weighted image and/or fluid-attenuated inversion recovery MR imaging, vascular stenosis severity was evaluated on computed tomography angiography images, and the level of cerebral perfusion was rated according to a staging system for abnormal cerebral perfusion based on CTP results. The relationships between the stenosis severity, cerebral perfusion level and ipsilateral WMHs severity were analyzed. A multivariate logistic regression analysis was performed to determine the factors independently influencing WMHs. Among 150 patients (mean age, 63.12±10.55 years), there was a statistically significant positive correlation between cerebral perfusion level and the severity of DWMHs and PWMHs (Gamma=0.561, p<.001; Gamma=0.600, p<.001), and a positive correlation between cerebral perfusion level and the severity of vascular stenosis (Gamma=0.495, p<.001).While, there was no statistically significant correlation between the severity of vascular stenosis and the severity of DWMHs and PWMHs (Gamma=0.188, p=.08; Gamma=0.196, p=.06). The multivariate logistic regression analysis results demonstrated that age (OR=1.047, 95% CI 1.003-1.093; p=.035), stroke/TIA history (OR=2.880, 95% CI 1.154-7.190; p=.023) and stage II of cerebral perfusion (OR=2.880, 95% CI 1.154-7.190; p=.023) were independent influencing factors on ipsilateral DWMHs. Age (OR=1.051, 95% CI 1.009-1.094; p=.018), and stage II of cerebral perfusion (OR=12.871, 95% CI 3.576-46.322; p<.001) were factors independently influencing ipsilateral PWMHs. White matter hyperintensities may be attributed to cerebral hypoperfusion secondary to vascular stenosis but not directly to the severity of stenosis in the large vessels of anterior circulation. Moreover, longitudinal studies with sequential imaging exams may further reveal the impact of cerebral perfusion secondary to vascular stenosis on the development and progression of WMHs.

Comparison of post contrast fluid attenuated inversion recovery, 3D T1-SPACE, and T1W MRI sequences with fat suppression in the diagnosis of infectious meningitis.

To assess the usefulness of post contrast Fluid attenuated inversion recovery (FLAIR), 3D T1-SPACE, and T1W magnetic resonance imaging (MRI) sequences with fat suppression in diagnosis of infectious meningitis. 75 patients with clinical suspicion of meningitis were evaluated with post contrast FLAIR (PC-FLAIR), post contrast T1-SPACE (PC-T1-SPACE), and post contrast T1WI (PC-T1WI). Sensitivity, specificity, positive predictive value, and negative predictive value of individual sequences were assessed. The sensitivity of PC-FLAIR (88.4%) was greater than PC-T1-SPACE (85.5%) and PC-T1WI (82.6%), considering cerebrospinal fluid (CSF) analysis as gold standard (p < 0.05). Kappa inter-rater agreement between two radiologists was 0.921 for PC-T1-SPACE, 0.921 for PC-T1WI, and 1.0 for PC-FLAIR with a p value <0.05. Both PC-T1-SPACE and PC-FLAIR performed equally in sulcal space enhancement. PC-T1-SPACE and PC-T1WI performed better in evaluation of pachymeningeal enhancement, ependymal enhancement in cases of ventriculitis, whereas PC-FLAIR was more sensitive in assessment of basal cistern enhancement and enhancement along the cerebellar folia. Meningeal enhancement could be better appreciated in PC-FLAIR image than PC-T1WI and PC-T1-SPACE. Enhancement in PC-T1-SPACE was comparable to that of PC-T1WI. Being a T1 based spin echo sequence, PC-T1-SPACE has all the advantages of PC-T1WI in addition to its ability to differentiate meningeal enhancement from leptomeningeal vessels. Hence, PC-T1WI can be replaced by PC-T1-SPACE and PC-FLAIR can be added to routine MRI protocol in suspected case of meningitis.

Emotional Lability as a Symptom of Extra-axial Posterior Fossa Tumors: a Case-Control Review of Neuroanatomy and Patient-Reported Quality of Life.

Introduction Emotional lability (EL), the uncontrollable and unmotivated expression of emotion, is a rare and distressing symptom of brainstem compression. In published case reports, EL from an extra-axial posterior fossa tumor was alleviated by tumor resection. The primary aim herein was to radiographically establish the degree of compression from mass lesions onto brainstem structures. Secondarily, we compared changes in patient-reported quality of life (QOL) pre- and postoperatively. Methods A retrospective review of posterior fossa tumors treated between 2002 and 2018 at Vancouver General Hospital revealed 11 patients with confirmed EL. Each case was matched to three controls. A lateral brainstem compression scale characterized mass effect at the level of the medulla, pons, and midbrain in preoperative axial T2-weighted fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) scans. Compression and clinical variables were compared between patient groups. Short Form-36 version 1 health surveys were retrospectively obtained from patient charts to compare pre- versus postoperative changes in survey scores between EL and control patients. Results EL symptoms ceased postoperatively for all EL patients. EL tumors exert greater compression onto the pons ( p = 0.03) and EL patients more commonly have cerebellar findings preoperatively ( p = 0.003). Patients with EL-causing tumors experienced greater improvement postoperatively in "Health Change" ( p = 0.05), which was maintained over time. Conclusion Findings suggest that compression onto the pons inhibits control over involuntary, stereotyped expression of emotion. This adds to evidence that EL may be attributed to cerebellum deafferentation from cortical and limbic structures through the basis pontis, leading to impaired modulation of emotional response. QOL results augment benefits of offering patients EL-alleviating tumor resection surgery.

White Matter Hyperintensities of the Corpus Callosum Are Associated With Clinical Severity in CADASIL.

In CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy), clinical severity is not related to the total burden of white matter hyperintensities (WMHs), presumably because of heterogeneous underlying tissue alterations. We aimed to investigate whether WMHs in the corpus callosum (WMHCC) are due to secondary degeneration and related to clinical severity. We evaluated data from 228 CADASIL patients included in an ongoing prospective cohort with available 3-dimensional fluid-attenuated inversion recovery magnetic resonance imaging sequences. We analyzed in a blind manner WMHCC and lacunes in presumably connected areas to determine whether WMHCC are related to secondary degeneration. We evaluated the links between WMHCC and the Mattis dementia rating scale and the modified Rankin Scale-widely used measures of global cognitive performances and disability, respectively. Linear regression models were adjusted for age, sex, level of education, brain volume, number of lacunes, and volume of WMH. Among 228 patients, only 105 (46%) had WMHCC while all had WMH in the rest of the white matter. In 74% of cases, WMHCC crossed a presumably connected nearby lacune, which was significantly higher than the expected value if the spatial distributions of WMHCC and nearby lacunes were unrelated (11%; P<0.001). Patients with WMHCC had worse Mattis dementia rating scale (median [P25-P75], 138 [122-142] versus 143 [140-143]; P<0.001) and worse modified Rankin Scale (2 [1-3] versus 1 [0-1]; P<0.001). In adjusted models, Mattis dementia rating scale was significantly associated with WMHCC (estimate, -6.2 [95% CI, -11.8 to -0.1]). In CADASIL, WMHCC are likely related to secondary degeneration and are independently related to clinical severity, in contrast to the total burden of WMH.

Peritumoural Oedema as a Predictor of Overall Survival for Patients with Posterior Fossa Metastases.

To analyse the relationship between peritumoural oedema volume and tumour volume in relation to the impact of metastatic posterior fossa tumour survival rates. An observational study. Umraniye Training and Research Hospital, İstanbul, Turkey, from 2011-2021. Fifty-six cancer patients who had been operated upon for cerebellar metastases were analysed retrospectively. To investigate the effect of oedema on survival, patients with a single cerebellar metastasis were evaluated retrospectively. Those patients had a single metastasis located in the cerebellum and did not receive radiotherapy or corticosteroids before surgery. OsiriX MD DICOM viewer was used to calculate the volumes of the tumour and the oedema using fluid-attenuated inversion recovery (FLAIR) and contrast-enhanced magnetic resonance imaging (MRI). The patients were separated into two groups, and the cut-off limit for the oedema to-tumour ratio was set to two. Survival analysis was performed on the two groups. When the primary sites of the tumours were evaluated, 60.7% were located in the lungs (n = 34), 10.7% were located in the breasts (n = 6), 10.7% were located in the gastrointestinal tract (n = 6), 7.1% were located in the renal region (n = 4), 5.4% were located in the gynaecologic tract (n = 3), and 5.4% were located in other parts of the body (n = 3). A univariate analysis showed that overall survival duration was significantly longer in the subgroup with breast cancer (83.3%) and in those patients with a peritumoural oedema volume to tumour volume ratio of less than two (27.6%, p <0.05). Negative prognostic factors were lung cancer and high peritumoural oedema volume. Significant peritumoural oedema was linked to a poor prognosis for cancer patients with a single cerebellar metastasis, especially with lung cancer as the primary source. Cerebellar metastases, Cerebellum, OsiriX MD, Tumour volume.