Tomoko Maekawa

Brain gray matter structural network in myotonic dystrophy type 1

This study aimed to investigate abnormalities in structural covariance network constructed from gray matter volume in myotonic dystrophy type 1 (DM1) patients by using graph theoretical analysis for further clarification of the underlying mechanisms of central nervous system involvement. Twenty-eight DM1 patients (4 childhood onset, 10 juvenile onset, 14 adult onset), excluding three cases from 31 consecutive patients who underwent magnetic resonance imaging in a certain period, and 28 age- and sex- matched healthy control subjects were included in this study. The normalized gray matter images of both groups were subjected to voxel based morphometry (VBM) and Graph Analysis Toolbox for graph theoretical analysis. VBM revealed extensive gray matter atrophy in DM1 patients, including cortical and subcortical structures. On graph theoretical analysis, there were no significant differences between DM1 and control groups in terms of the global measures of connectivity. Betweenness centrality was increased in several regions including the left fusiform gyrus, whereas it was decreased in the right striatum. The absence of significant differences between the groups in global network measurements on graph theoretical analysis is consistent with the fact that the general cognitive function is preserved in DM1 patients. In DM1 patients, increased connectivity in the left fusiform gyrus and decreased connectivity in the right striatum might be associated with impairment in face perception and theory of mind, and schizotypal-paranoid personality traits, respectively.

Thalamic hypoperfusion and disrupted cerebral blood flow networks in idiopathic generalized epilepsy: Arterial spin labeling and graph theoretical analysis

PURPOSE The aim of this study was to investigate interictal cerebral blood flow (CBF) distributions and graph theoretical networks in idiopathic generalized epilepsy (IGE) using arterial spin labeling (ASL) imaging and anatomical covariance methods of graph theoretical analysis. MATERIAL AND METHODS We recruited 19 patients with IGE and 19 age-/gender-matched healthy controls. Their CBF images were obtained by pseudo-continuous ASL imaging and compared using statistical parametric mapping 8 software (SPM8) and Graph Analysis Toolbox (GAT). RESULTS The ASL imaging could detect interictal hypoperfusion in the thalamus, upper midbrain, and left cerebellum in IGE. Additionally, the graph theoretical analyses revealed characteristic findings of the CBF network of IGE, including significantly reduced resilience to attacks and changes of regional clustering especially in the bilateral temporo-occipital areas and lateral frontal lobes. There was no significance in the comparisons of network metrics. CONCLUSION These findings could contribute to a better understanding of the pathophysiology of IGE.

The Advantage of Synthetic MRI for the Visualization of Anterior Temporal Pole Lesions on Double Inversion Recovery (DIR), Phase-sensitive Inversion Recovery (PSIR), and Myelin Images in a Patient with CADASIL

Received: August 8, 2017 | Accepted: October 25, 2017 Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare, hereditary form of small-vessel disease caused by mutations in the NOTCH3 gene at q13.1 on chromosome 19, which result in strokes in young adults. Multiple subcortical lacunar infarcts and diffuse leukoencephalopathy are typical findings in patients with CADASIL. Anterior temporal pole and external capsule lesions are known to have high sensitivity for CADASIL, with anterior temporal pole lesions showing higher specificity.1 SyMRI is a MRI technique that enables rapid simultaneous quantification of T1 and T2 relaxation times, and proton density.2 Based on these absolute values, any contrast-weighted image with optional inversion recovery time (TI) can be created by synthetic MRI. The volume of myelin can also be estimated from the acquired quantitative values. SyMRI has been evaluated for use in patients with diseases such as multiple sclerosis and Sturge-Weber Syndrome, with promising results.3,4 Here, we present a case of a 40-year-old man with proven NOTCH3 mutation who was referred to our hospital with an episode of dysarthria. Radiological investigations were performed, including diffusion-weighted MRI (image not shown), which revealed an acute infarct in the left centrum semiovale, explaining the patient’s symptom. As part of our hospital’s routine protocol, SyMRI was also performed using a 3T MRI system (Discovery MR750w 3.0T; GE Healthcare, Milwaukee, WI, USA). Acquisition time was 7 min 12 s. Synthetic images were created using SyMRI software (ver 8.0, SyntheticMR AB, Linköping, Sweden). Synthetic fluid attenuated inversion recovery (FLAIR) (Fig. 1A; TR 15,000 ms; TE 100 ms; TI 3000 ms) and double inversion recovery (DIR) (Fig. 1B; TR 15,000 ms; TE 100 ms; initial TI 470 ms; second TI 3750 ms) images showed hyperintense lesions in both anterior temporal poles, with these lesions more clearly visualized, particularly in the left anterior temple pole, in the DIR images. These lesions were also visualized on synthetic T1-weighted (Fig. 1C; TR 500 ms; TE 10 ms) and phasesensitive inversion recovery (PSIR) (Fig. 1D; TR 6000 ms; TE 10 ms; TI 500 ms) images, with the PSIR image clearer than the T1-weighted image, especially in the left anterior pole. A myelin map overlaid on the synthetic T2-weighted image (Fig. 1E; TR 4500 ms; TE 100 ms) clearly showed the decrease in volume of myelin in both anterior temporal poles. The synthetic FLAIR image showed bilateral external capsule lesions (Fig. 2A). The decrease in volume of myelin was clearly visualized bilaterally in the external capsules using the myelin map overlaid on the T2-weighted image (Fig. 2B). This case demonstrates the usefulness of SyMRI in generating contrast-weighted images and enabling measurement of myelin volume after MRI acquisition. Synthetic DIR and PSIR may increase sensitivity for detecting anterior temporal pole lesions, and decreases in volume of myelin can be visualized on a myelin map. Detection of these lesions may be useful for differential early diagnosis of CADASIL.

Thalamic involvement determined using VSRAD advance on MRI and easy Z-score analysis of 99mTc-ECD-SPECT in Gerstmann-Sträussler-Scheinker syndrome with P102L mutation

Gerstmann-Sträussler-Scheinker syndrome caused by the P102L mutation in the prion protein gene (GSS102) is usually characterized by the onset of slowly progressive cerebellar ataxia, with dementia occurring much later. Because of the relatively long disease course and the prominence of progressive cerebellar ataxia in the early stage, GSS102 is often misdiagnosed as other neurodegenerative disorders. We present two cases of genetically proven GSS102L, both of which present with atrophy and decreased blood flow of the thalamus as determined by voxel-based specific regional analysis system for Alzheimers disease (VSRAD) advance software and easy Z-score analysis for 99mTc-ethyl cysteinate dimer-SPECT, respectively. These thalamic abnormalities have not been fully evaluated to date, and detecting them might be useful for differentiating GSS102 from other neurodegenerative disorders.

Myelin Measurement: Comparison between Simultaneous Tissue Relaxometry, Magnetization Transfer Saturation Index, and T1w/T2w Ratio Methods

Magnetization transfer (MT) imaging has been widely used for estimating myelin content in the brain. Recently, two other approaches, namely simultaneous tissue relaxometry of R1 and R2 relaxation rates and proton density (SyMRI) and the ratio of T1-weighted to T2-weighted images (T1w/T2w ratio), were also proposed as methods for measuring myelin. SyMRI and MT imaging have been reported to correlate well with actual myelin by histology. However, for T1w/T2w ratio, such evidence is limited. In 20 healthy adults, we examined the correlation between these three methods, using MT saturation index (MTsat) for MT imaging. After calibration, white matter (WM) to gray matter (GM) contrast was the highest for SyMRI among these three metrics. Even though SyMRI and MTsat showed strong correlation in the WM (r = 0.72), only weak correlation was found between T1w/T2w and SyMRI (r = 0.45) or MTsat (r = 0.38) (correlation coefficients significantly different from each other, with p values < 0.001). In subcortical and cortical GM, these measurements showed moderate to strong correlations to each other (r = 0.54 to 0.78). In conclusion, the high correlation between SyMRI and MTsat indicates that both methods are similarly suited to measure myelin in the WM, whereas T1w/T2w ratio may be less optimal.

A structural MRI study of cholinergic pathways and cognition in multiple sclerosis

Background White matter hyperintensities (WMH) in the cholinergic pathways are associated with cognitive performance in Alzheimers disease. This study aimed to evaluate the relationship between the volume reduction of cholinergic pathways and cognitive function in patients with multiple sclerosis (MS). Methods Thirty-two MS patients underwent a brain MRI and cognitive measurements including the Mini-Mental State Examination (MMSE) and the Japanese version of the Montreal Cognitive Assessment (MoCA-J). The extent of WMH within the cholinergic pathways was assessed using the Cholinergic Pathways Hyperintensities Scale (CHIPS). Computerized WMH volumes were also obtained. FreeSurfer was used to measure regional volumes including the cortical and subcortical volumes. The correlations among the CHIPS, the WMH volume, and the clinical data were assessed, in addition to the correlations between the cognitive scores and regional volumes measured by FreeSurfer. Results The CHIPS score and the WMH volume were strongly positively correlated with each other (r = 0.87, P < 0.001). The CHIPS score had significantly negative correlations with the MMSE (r = − 0.49, P = 0.003) and the MoCA-J (r = − 0.47, P = 0.005) results. The WMH volume had significantly negative correlations with the MMSE (r = − 0.54, P = 0.001) and the MoCA-J (r = − 0.57, P < 0.001) results. In the analysis by FreeSurfer, both the MMSE and MoCA-J scores had significant positive correlations only with the volume of the corpus callosum. Conclusions The CHIPS score tended to be less sensitive to the WMH volume in cognitive function evaluation, although the difference did not reach the level of statistical significance. Thus the CHIPS method may not be as effective in MS patients.

MR findings in the substantia nigra on phase difference enhanced imaging in neurodegenerative parkinsonism

INTRODUCTION In Parkinsons disease (PD) patients, magnetic resonance (MR) imaging studies using phase difference enhanced imaging (PADRE) and susceptibility-weighted imaging (SWI) showed the obscuration of the boundary between the crural fibers and substantia nigra, and the absence of dorsolateral nigral hyperintensity, respectively. PADRE images have not been evaluated in other types of neurodegenerative parkinsonism, and PADRE and SWI images have not been compared. Here we evaluated PADRE and SWI images in patients with progressive supranuclear palsy (PSP), multiple system atrophy (MSA), or PD and controls, and we compared the diagnostic values. METHODS PADRE and SWI-like MR images were visually assessed focusing on the substantia nigra in 39 PD patients, eight with PSP, 13 with MSA, and 34 normal controls. RESULTS The obscuration of the boundary between the crural fibers and substantia nigra on PADRE was observed in: the PD group, 62%; PSP, 100%; MSA, 60%, and controls, 19%. The overall collect classification for neurodegenerative parkinsonism was 74%. The absence of dorsolateral nigral hyperintensity on SWI-like images was present in: PD, 97%; PSP, 100%; MSA, 67%; and controls, 6%, resulting in the overall correct classification of 96%. CONCLUSIONS The MR feature on PADRE was observed not only in PD but also in other neurodegenerative parkinsonism, especially in PSP with high sensitivity. The finding in substantia nigra on SWI had greater discrimination power than that of PADRE in neurodegenerative parkinsonism, especially in PD.

Correlations between dopamine transporter density measured by 123I-FP-CIT SPECT and regional gray matter volume in Parkinson’s disease

PurposeParkinson’s disease (PD) is caused by a selective degeneration of dopamine neurons. The relationship between dopamine transporter (DAT) density and gray matter volume has been unclear. Here we investigated the voxelwise correlation between gray matter volume and DAT binding measured by 123I-N-ω-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl)nortropane (123I-FP-CIT) single-photon emission computed tomography (SPECT; DaTscan™ imaging) in PD.Materials and methodsThirty-one male patients with PD were examined with MRI and DaTscan. To measure nigrostriatal dopaminergic degeneration in PD, the specific binding ratio (SBR) of the striatum was obtained by DaTscan. Voxel-based morphometry (VBM) of 3D T1-weighted images was used to evaluate the relationships between the regional gray matter volume and the SBR in the striatum.ResultsThere were significant positive correlations between the SBR and the gray matter volume in the right pulvinar and posterior middle temporal gyrus and a trend level in the left pulvinar, all of which are associated with the second visual pathway.ConclusionThe nigrostriatal dopaminergic degeneration might affect the secondary visual pathway, leading to visual dysfunctions in PD.