Hung-Chieh Chen

Differences between spinocerebellar ataxias and multiple system atrophy-cerebellar type on proton magnetic resonance spectroscopy.

Purpose A broad spectrum of diseases can manifest cerebellar ataxia. In this study, we investigated whether proton magnetic resonance spectroscopy (MRS) may help differentiate spinocerebellar ataxias (SCA) from multiple systemic atrophy- cerebellar type (MSA-C). Material and Methods This prospective study recruited 156 patients with ataxia, including spinocerebellar ataxia (SCA) types 1, 2, 3, 6 and 17 (N = 94) and MSA-C (N = 62), and 44 healthy controls. Single voxel proton MRS in the cerebellar hemispheres and vermis were measured. The differences were evaluated using nonparametric statistic tests. Results When compared with healthy controls, the cerebellar and vermis NAA/Cr and NAA/Cho were lower in all patients(p<0.002). The Cho/Cr was lower in SCA2 and MSA-C (p<0.0005). The NAA/Cr and Cho/Cr were lower in MSA-C or SCA2 comparing with SCA3 or SCA6. The MRS features of SCA1 were in between (p<0.018). The cerebellar NAA/Cho was lower in SCA2 than SCA1, SCA3 or SCA6 (p<0.04). The cerebellar NAA/Cho in MSA-C was lower than SCA3 (p<0.0005). In the early stages of diseases (SARA score<10), significant lower NAA/Cr and NAA/Cho in SCA2, SCA3, SCA6 or MSA-C were observed comparing with healthy controls (p<0.017). The Cho/Cr was lower in MSA-C or SCA2 (p<0.0005). Patients with MSA-C and SCA2 had lower NAA/Cr and Cho/Cr than SCA3 or SCA6 (p<0.016). Conclusion By using MRS, significantly lower NAA/Cr, Cho/Cr and NAA/Cho in the cerebellar hemispheres and vermis were found in patients with ataxia (SCAs and MSA-C). Rapid neuronal degeneration and impairment of membrane activities were observed more often in patients with MSA-C than those with SCA, even in early stages. MRS could also help distinguish between SCA2 and other subtypes of SCAs. MRS ratios may be of use as biomarkers in early stages of disease and should be further assessed in a longitudinal study.

Increased myo-inositol level in dorsolateral prefrontal cortex in migraine patients with major depression.

Background Although the comorbidity between migraine and major depressive disorder (MDD) has been recognized, the pathophysiology remains unclear. The dorsolateral prefrontal cortex (DLPFC) is a well-known neural substrate for MDD. We investigated the relationship between brain metabolites in DLPFC and comorbid MDD in migraine patients. Methods We recruited migraine patients from a tertiary headache clinic. A board-certified psychiatrist conducted a structured interview for MDD diagnosis. The severity of depression was evaluated by the Beck Depression Inventory (BDI). Thirty migraine patients (five men, 25 women; mean age: 40.4 ± 12.4 years) completed the study, and 16 of them were diagnosed with MDD. All patients underwent a magnetic resonance spectroscopy (MRS) examination focusing on bilateral DLPFC. The ratios of N-acetylaspartate (NAA), choline (Cho), and myo-inositol (mI) to total creatine (tCr) were compared between migraine patients with and without MDD, and were correlated with BDI scores. Results Relative to patients without MDD, migraine patients with MDD had higher mI/tCr ratios in the bilateral DLPFC (p = 0.02, left; p = 0.02, right, Mann-Whitney U test). The mI/tCr ratios in the right DLPFC were positively correlated with BDI scores (r = 0.52, p = 0.003). The NAA/tCr and Cho/tCr ratios did not differ between migraine patients with and without MDD. Conclusion Increased mI/tCr within the DLPFC might be associated with the presence of MDD in migraine patients.

Association between Proton Magnetic Resonance Spectroscopy Measurements and CAG Repeat Number in Patients with Spinocerebellar Ataxias 2, 3, or 6

The aim of this study was to correlate magnetic resonance spectroscopy (MRS) measurements, including that for the N-acetyl aspartate (NAA)/creatine (Cr) ratio in the vermis (denoted V-NAA), right cerebellar hemisphere (R-NAA), and left (L-NAA) cerebellar hemisphere, with the clinical scale for the assessment and rating of ataxia (SARA) score for patients with spinocerebellar ataxia (SCA) types 2, 3, and 6. A total of 24 patients with SCA2, 48 with SCA3, and 16 with SCA6 were recruited; 12 patients with SCA2, 43 with SCA3, and 8 with SCA6 underwent detailed magnetic resonance neuroimaging. Forty-four healthy, age-matched individuals without history of neurologic disease served as control subjects. V-NAA and patient age were used to calculate the predicted age at which a patient with SCA2 or SCA3 would reach an onset V-NAA value. Results showed the following: the NAA/Cr ratio decreased with increasing age in patients with SCA but not in control subjects; the SARA score increased progressively with age and duration of illness; V-NAA showed a better correlation with SARA score than R-NAA in patients with SCA2 or SCA3; the ratio of age to V-NAA correlated well with CAG repeat number; the retrospectively predicted age of onset for SCA2 and SCA3 was consistent with patient-reported age of onset; R-NAA showed a better correlation with SARA score than V-NAA in patients with SCA6; V-NAA and R-NAA correlated with clinical severity (SARA score) in patients with SCA. The correlation between CAG repeat number and age could be expressed as a simple linear function, which might explain previous observations claiming that the greater the CAG repeat number, the earlier the onset of illness and the faster the disease progression. These findings support the use of MRS values to predict age of disease onset and to retrospectively evaluate the actual age of disease onset in SCA.

The merit of proton magnetic resonance spectroscopy in the longitudinal assessment of spinocerebellar ataxias and multiple system atrophy-cerebellar type

BackgroundSpinocerebellar ataxia (SCA) and multiple system atrophy-cerebellar type (MSA-C) often present with similar clinical manifestations in the beginning. Magnetic resonance spectroscopy (MRS) has been proved to be a useful tool to help differentiate different types of SCA and MSA-C on cross-sectional studies. However, longitudinal changes of the MRS metabolites in these subjects have never been reported. The purpose of this study was to track the longitudinal evolution of the MRS metabolites in these patients and to ascertain the correlation between clinical severity measured by Scale of the Assessment and Rating of Ataxia (SARA) and MRS metabolites.ResultsSignificant reductions of NAA/Cr and NAA/Cho in the cerebellar hemispheres in all patients and lower Cho/Cr in the cerebellar hemispheres in patients with SCA2 or MSA-C were found at all times. At initial assessments, patients with MSA-C or SCA2 tended to have lower NAA/Cr and Cho/Cr in the cerebellar hemispheres than those with SCA3 or SCA6. At follow-ups, patients with SCA2 or MSA-C had a lower NAA/Cr in cerebellar hemispheres than those with SCA3 or SCA6. Patients with MSA-C had a lower NAA/Cr in the vermis and Cho/Cr in the cerebellar hemispheres than those with SCA2 at the start, and had a lower NAA/Cr in cerebellar hemispheres than those with SCA2 at follow-ups.ConclusionCharacteristic patterns of neurodegenerative evolution were observed in patients with disparate SCAs and MSA-C using MRS and SARA. A continual impairment of neuronal integrity was observed in all groups of patients. The longitudinal changes of MRS metabolites and SARA scores were most striking in patients with SCA2 and MSA-C. Although the changes in the metabolites on MRS may still be used to help understand the pathophysiology of ataxia disorders, they are short of being a good biomarker.

Usefulness of phase-contrast magnetic resonance imaging for diagnosis and treatment evaluation in patients with SIH

Background Most diagnostic tools for spontaneous intracranial hypotension (SIH) are either invasive or occasionally inconsistent with the clinical condition. In this study, we examined the cerebrospinal fluid (CSF) dynamics in SIH using phase-contrast magnetic resonance (PC-MR) imaging. Materials and method Seventeen SIH patients and 32 healthy individuals, matched by sex and age, were recruited. Each person underwent brain and PC-MR imaging using 3-Tesla MRI. We evaluated the differences in image parameters among patients during the initial and recovery stages against the status of the control group. Results SIH patients had lower CSF flow-volume, flux, peak velocity, and higher systolic-to-diastolic time ratio, as well as systolic-to-diastolic volume ratio compared to the control group and the conditions when they recovered. The flow time and volume of the diastolic phase markedly increased after treatment. The discriminating power of PC-MR for SIH was good. Diffuse pachymeningeal enhancement and venous engorgement were present when their PC-MR values were lower than the cut-off values for SIH diagnosis. The headache scores correlated with the peak velocity and pituitary volume. Conclusion Noninvasive PC-MR could provide valid parameters for diagnosis and treatment follow-up in SIH patients. It may be more sensitive than conventional brain MRI.

Robust volume assessment of brain tissues for 3-dimensional fourier transformation MRI via a novel multispectral technique.

A new TRIO algorithm method integrating three different algorithms is proposed to perform brain MRI segmentation in the native coordinate space, with no need of transformation to a standard coordinate space or the probability maps for segmentation. The method is a simple voxel-based algorithm, derived from multispectral remote sensing techniques, and only requires minimal operator input to depict GM, WM, and CSF tissue clusters to complete classification of a 3D high-resolution multislice-multispectral MRI data. Results showed very high accuracy and reproducibility in classification of GM, WM, and CSF in multislice-multispectral synthetic MRI data. The similarity indexes, expressing overlap between classification results and the ground truth, were 0.951, 0.962, and 0.956 for GM, WM, and CSF classifications in the image data with 3% noise level and 0% non-uniformity intensity. The method particularly allows for classification of CSF with 0.994, 0.961 and 0.996 of accuracy, sensitivity and specificity in images data with 3% noise level and 0% non-uniformity intensity, which had seldom performed well in previous studies. As for clinical MRI data, the quantitative data of brain tissue volumes aligned closely with the brain morphometrics in three different study groups of young adults, elderly volunteers, and dementia patients. The results also showed very low rates of the intra- and extra-operator variability in measurements of the absolute volumes and volume fractions of cerebral GM, WM, and CSF in three different study groups. The mean coefficients of variation of GM, WM, and CSF volume measurements were in the range of 0.03% to 0.30% of intra-operator measurements and 0.06% to 0.45% of inter-operator measurements. In conclusion, the TRIO algorithm exhibits a remarkable ability in robust classification of multislice-multispectral brain MR images, which would be potentially applicable for clinical brain volumetric analysis and explicitly promising in cross-sectional and longitudinal studies of different subject groups.

Patterns of cerebrospinal fluid (CSF) distribution in patients with spontaneous intracranial hypotension: Assessed with magnetic resonance myelography

Background Diagnosis of spontaneous intracranial hypotension (SIH) relies on the ability of medical staff to recognize cerebrospinal fluid (CSF) leakage at the spine. However, difficulties with interobserver discrepancy sometimes occurred while reading magnetic resonance myelography (MRM) because clear image definition was lacking. In this study, we tried to determine which pattern of CSF distribution is more reliable for diagnosis of CSF leakage by using MRM. Methods From January 2012 to August 2014, 19 SIH patients and 27 healthy controls (HC) were recruited into our study; 10 of the 19 patients were recovered (SIH‐R) after treatment. Whole spine MRM was performed using the 3D‐SPACE (three‐dimensional sampling perfection with application‐optimized contrasts using different flip‐angle evolutions) sequence, and interpreted by two experienced neuroradiologists. Two 4‐point classification systems of CSF distribution were used to evaluate the three‐dimensional maximum intensity projection (3D MIP) and the thin‐slice axial multiplanar reconstruction (MPR) images, respectively. Results The interobserver agreement between the two readers interpreting the 3D MIP and thin‐slice axial MPR MRM were moderate to good (&kgr; = 0.60–0.78). Grade 3 of 3D MIP and Type D of axial MPR MRM were only noticed in the SIH. Overall, Grade 3 of MIP and Type D of MPR showed significant difference (p < 0.008) between the SIH and the HC in the whole spine. Type C at the T‐spine was more frequently noted in the SIH than in the HC (p < 0.038). By using “Grade 3”, “Type D”, “Type D and Type C at T‐spine” as the diagnostic criteria of CSF leakage, the sensitivity, specificity, positive predict value (PPV), and negative predict value (NPV) were all > 70%. Conclusion Grade 3 on 3D MIP and Type D on axial MPR MRM were definite criteria of MRM for localizing CSF leakage, and Type C in the T‐spine was a probable leakage sign with high sensitivity and NPV.

Magnetic Resonance Angiography in the Diagnosis of Cerebral Arteriovenous Malformation and Dural Arteriovenous Fistulas: Comparison of Time-Resolved Magnetic Resonance Angiography and Three Dimensional Time-of-Flight Magnetic Resonance Angiography

Background Traditional digital subtraction angiography (DSA) is currently the gold standard diagnostic method for the diagnosis and evaluation of cerebral arteriovenous malformation (AVM) and dural arteriovenous fistulas (dAVF). Objectives The aim of this study was to analyze different less invasive magnetic resonance angiography (MRA) images, time-resolved MRA (TR-MRA) and three-dimensional time-of-flight MRA (3D TOF MRA) to identify their diagnostic accuracy and to determine which approach is most similar to DSA. Patients and Methods A total of 41 patients with AVM and dAVF at their initial evaluation or follow-up after treatment were recruited in this study. We applied time-resolved angiography using keyhole (4D-TRAK) MRA to perform TR-MRA and 3D TOF MRA examinations simultaneously followed by DSA, which was considered as a standard reference. Two experienced neuroradiologists reviewed the images to compare the diagnostic accuracy, arterial feeder and venous drainage between these two MRA images. Inter-observer agreement for different MRA images was assessed by Kappa coefficient and the differences of diagnostic accuracy between MRA images were evaluated by the Wilcoxon rank sum test. Results Almost all vascular lesions (92.68%) were correctly diagnosed using 4D-TRAK MRA. However, 3D TOF MRA only diagnosed 26 patients (63.41%) accurately. There were statistically significant differences regarding lesion diagnostic accuracy (P = 0.008) and venous drainage identification (P < 0.0001) between 4D-TRAK MRA and 3D TOF MRA. The results indicate that 4D-TRAK MRA is superior to 3D TOF MRA in the assessment of lesions. Conclusion Compared with 3D TOF MRA, 4D-TRAK MRA proved to be a more reliable screening modality and follow-up method for the diagnosis of cerebral AVM and dAVF.

Imaging Appearance of Magnetic Resonance Myelography in Normal Population: Employing Three-dimensional Sampling Perfection with Application Optimized Contrasts Using Different Flip-angle Evolutions (3D-SPACE) Sequence

Characterizing the normal distribution of cerebrospinal fluid (CSF) in the spine is crucial for an accurate assessment of CSF leakage and other abnormalities. Magnetic resonance myelography (MRM) is a noninvasive diagnostic method that is commonly used to evaluate the spinal distribution of CSF. Our aim was to evaluate the anatomical distribution of CSF in the spine of healthy individuals, by MRM using the three-dimensional sampling perfection with amplification-optimized contrasts using flip-angle evolutions (3D-SPACE) sequence. Twenty-one healthy volunteers underwent whole-spine MRM imaging using the 3D-SPACE sequence. MRM images were reconstructed with 5-mm axial multiplanar reconstruction (MPR) and maximum intensity projection (MIP) at each spine level. Two radiologists evaluated CSF distribution from the spinal canal in the MPR and MIP images, using 7-point (types A-G) and 3-point (grades 0-3) classification systems, respectively. Inter-reader agreement was calculated with the kappa coefficient (K). Reader 1/reader 2 evaluated 46/53, 67/57, 4/6, 0/0, 0/0, 7/5, and 2/5 cervical spine (C-spine)-level MPR images corresponding to types A-G, respectively (K = 0.74). Numbers at the thoracic spine (T-spine) level were 1851186, 41144, 8/5, 0/0, 0/0, 16/11, and 2/6, respectively (K = 0.69), and at the lumbar spine (L-spine) level were 46/58, 25/23, 9/5, 0/0, 0/0, 19/13, and 6/6, respectively (K = 0.50). Inter-reader agreement for MPR images at the whole-spine level was considered good (K = 0.69). Reader 1/reader 2 evaluated 0/0, 13/13, 8/8, and % MIP images at the C-spine level corresponding to grades 0-3, respectively (K = 0.80). Numbers at the T-spine level were 10/14, 8/5, 3/2, and 0/0, respectively (K = 0.67), and at the L-spine level were 5/2, 10/8, 6/11, and 0/0, respectively (K = 0.26). Inter-reader agreement for MIP images at the whole-spine level was considered good (K = 0.61). In conclusion, T2-weighted MRM with 3D-SPACE sequence imaging can be a useful technique to detect the normal distribution of CSF in the spinal canal. Understanding the normal distribution of CSF in the spinal canal is necessary to achieve an accurate diagnosis of CSF leakage.

Noninvasive assessment of intracranial elastance and pressure in spontaneous intracranial hypotension by MRI: MR Intracranial Pressure for SIH

Spontaneous intracranial hypotension (SIH) is often misdiagnosed, and can lead to severe complications. Conventional MR sequences show a limited ability to aid in this diagnosis. MR‐based intracranial pressure (MR‐ICP) may be able to detect changes of intracranial elastance and pressure.