Christopher Magnano

Abnormal subcortical deep-gray matter susceptibility-weighted imaging filtered phase measurements in patients with multiple sclerosis: a case-control study.

OBJECTIVE To investigate abnormal phase on susceptibility-weighted imaging (SWI)-filtered phase images indicative of iron content, in subcortical deep-gray matter (SDGM) of multiple sclerosis (MS) patients and healthy controls (HC), and to explore its relationship with MRI outcomes. METHODS 169 relapsing-remitting (RR) and 64 secondary-progressive (SP) MS patients, and 126 age- and sex-matched HC were imaged on a 3T scanner. Mean phase of the abnormal phase tissue (MP-APT), normal phase tissue volume (NPTV) and normalized volume were determined for total SDGM, caudate, putamen, globus pallidus, thalamus, pulvinar nucleus of thalamus (PVN), hippocampus, amygdala, nucleus accumbens, red nucleus and substantia nigra. 63 HC were used for establishment of normal reference phase values, while additional 63 HC were used for blinded comparisons with MS patients. RESULTS Increased MP-APT, decreased normalized volume and decreased NPTV were detected in total SDGM, caudate, putamen, globus pallidus, thalamus and PVN in MS patients compared to HC (p<.0004). MS patients also showed decreased volume in hippocampus (<.0001) and decreased NPTV in the hippocampus, amygdala and accumbens (<.0004). SPMS patients had increased MP-APT, decreased volume and decreased NPTV in total SDGM, caudate and amygdala compared to RRMS (p<.005), while individual measure differences were also detected in putamen, thalamus, hippocampus and accumbens (p<.006). RRMS patients showed a significant relationship between increased MP-APT and increased lesion burden and more advanced brain atrophy (p<.004). CONCLUSIONS Abnormal phase, indicative of higher iron content was significantly increased in MS patients compared to HC, and was related to more severe lesion burden and brain atrophy.

Use of MR venography for characterization of the extracranial venous system in patients with multiple sclerosis and healthy control subjects.

PURPOSE To investigate the differences in the extracranial venous system in patients with multiple sclerosis (MS) and healthy control (HC) subjects by using magnetic resonance (MR) venography. MATERIALS AND METHODS This HIPAA-compliant, prospective study was approved by the local institutional review board, and all participants gave informed consent. Fifty-seven patients, 41 (72%) with relapsing-remitting MS and 16 (28%) with secondary-progressive MS, and 21 HC subjects were imaged with a 3-T MR unit by using two-dimensional (2D) time-of-flight (TOF) and three-dimensional (3D) time-resolved imaging of contrast kinetics (TRICKS) sequences. In addition, six MS patients and six HC subjects underwent two sequential MR venographic examinations during 1 week to test image-reimage reproducibility. The morphologic features of internal jugular vein flow were classified as absent, pinpoint, flattened, crescentic, or ellipsoidal flow. Only absent and pinpoint flow were considered abnormal. The flow of the vertebral veins was classified as absent or present. The prominence of collateral neck veins and venous asymmetries between the left and right sides were assessed. Differences among groups were tested with a two-tailed Mann-Whitney two-sample rank-sum test. RESULTS No significant differences in morphologic features of flow in the internal jugular veins and vertebral veins were found between MS patients and HC subjects in any of the examined MR venographic parameters. No differences in asymmetry or prominence were found between MS patients and HC subjects. There was modest agreement (κ = 0.67) between 2D TOF and 3D TRICKS sequences. Image-reimage reproducibility showed modest agreement (κ = 0.66) for 2D TOF and low agreement for 3D TRICKS (κ = 0.33). CONCLUSION No significant differences in the extracranial venous systems between MS patients and HC subjects were detected by using MR venography. Standardized guidelines are needed to define parameters for the presence of venous anomalies.

Hypoperfusion of brain parenchyma is associated with the severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a cross-sectional preliminary report

BackgroundSeveral studies have reported hypoperfusion of the brain parenchyma in multiple sclerosis (MS) patients. We hypothesized a possible relationship between abnormal perfusion in MS and hampered venous outflow at the extracranial level, a condition possibly associated with MS and known as chronic cerebrospinal venous insufficiency (CCSVI).MethodsWe investigated the relationship between CCSVI and cerebral perfusion in 16 CCSVI MS patients and 8 age- and sex-matched healthy controls. Subjects were scanned in a 3-T scanner using dynamic susceptibility, contrast-enhanced, perfusion-weighted imaging. Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the gray matter (GM), white matter (WM) and the subcortical GM (SGM). The severity of CCSVI was assessed according to the venous hemodynamic insufficiency severity score (VHISS) on the basis of the number of venous segments exhibiting flow abnormalities.ResultsThere was a significant association between increased VHISS and decreased CBF in the majority of examined regions of the brain parenchyma in MS patients. The most robust correlations were observed for GM and WM (r = -0.70 to -0.71, P < 0.002 and P corrected = 0.022), and for the putamen, thalamus, pulvinar nucleus of thalamus, globus pallidus and hippocampus (r = -0.59 to -0.71, P < 0.01 and P corrected < 0.05). No results for correlation between VHISS and CBV or MTT survived multiple comparison correction.ConclusionsThis pilot study is the first to report a significant relationship between the severity of CCSVI and hypoperfusion in the brain parenchyma. These preliminary findings should be confirmed in a larger cohort of MS patients to ensure that they generalize to the MS population as a whole. Reduced perfusion could contribute to the known mechanisms of virtual hypoxia in degenerated axons.

Iron deposition in multiple sclerosis lesions measured by susceptibility-weighted imaging filtered phase: A case control study

To investigate phase lesions identified on susceptibility‐weighted imaging (SWI)‐filtered phase images in patients with multiple sclerosis (MS), clinically isolated syndrome (CIS) and healthy controls (HC). To relate phase lesion characteristics to other clinical and MRI outcomes.

Decreased brain venous vasculature visibility on susceptibility-weighted imaging venography in patients with multiple sclerosis is related to chronic cerebrospinal venous insufficiency

BackgroundThe potential pathogenesis between the presence and severity of chronic cerebrospinal venous insufficiency (CCSVI) and its relation to clinical and imaging outcomes in brain parenchyma of multiple sclerosis (MS) patients has not yet been elucidated. The aim of the study was to investigate the relationship between CCSVI, and altered brain parenchyma venous vasculature visibility (VVV) on susceptibility-weighted imaging (SWI) in patients with MS and in sex- and age-matched healthy controls (HC).Methods59 MS patients, 41 relapsing-remitting and 18 secondary-progressive, and 33 HC were imaged on a 3T GE scanner using pre- and post-contrast SWI venography. The presence and severity of CCSVI was determined using extra-cranial and trans-cranial Doppler criteria. Apparent total venous volume (ATVV), venous intracranial fraction (VIF) and average distance-from-vein (DFV) were calculated for various vein mean diameter categories: < .3 mm, .3-.6 mm, .6-.9 mm and > .9 mm.ResultsCCSVI criteria were fulfilled in 79.7% of MS patients and 18.2% of HC (p < .0001). Patients with MS showed decreased overall ATVV, ATVV of veins with a diameter < .3 mm, and increased DFV compared to HC (all p < .0001). Subjects diagnosed with CCSVI had significantly increased DFV (p < .0001), decreased overall ATVV and ATVV of veins with a diameter < .3 mm (p < .003) compared to subjects without CCSVI. The severity of CCSVI was significantly related to decreased VVV in MS (p < .0001) on pre- and post-contrast SWI, but not in HC.ConclusionsMS patients with higher number of venous stenoses, indicative of CCSVI severity, showed significantly decreased venous vasculature in the brain parenchyma. The pathogenesis of these findings has to be further investigated, but they suggest that reduced metabolism and morphological changes of venous vasculature may be taking place in patients with MS.

Assessing Abnormal Iron Content in the Deep Gray Matter of Patients with Multiple Sclerosis versus Healthy Controls

BACKGROUND AND PURPOSE: It is well known that patients with MS tend to have abnormal iron deposition in and around the MS plaques, in the basal ganglia and the THA. In this study, we used SWI to quantify iron content in patients with MS and healthy volunteers. MATERIALS AND METHODS: Fifty-two patients with MS were recruited to assess abnormal iron content in their basal ganglia and THA structures. One hundred twenty-two healthy subjects were recruited to establish a baseline of normal iron content in deep GM structures. Each structure was separated into 2 regions: a low-iron-content region and a high-iron-content region. The average phase, the percentage area, and the total phase of the high-iron-content region were evaluated. A weighting was also assigned to each subject depending on the level of iron content and its deviation from the normal range. RESULTS: A clear separation between iron content in healthy subjects versus patients with MS was seen. For healthy subjects 13% and for patients with MS 65% showed an iron-weighting factor >3 SDs from the normal mean (P < .05). The results for those patients younger than 40 years are even more impressive. In these cases, only 1% of healthy subjects and 67% of patients with RRMS showed abnormally high iron content. CONCLUSIONS: Iron-weighting factors in the basal ganglia, THA, and the midbrain appeared to be abnormal in roughly two-thirds of patients with MS as measured by SWI.

Iron deposition on SWI-filtered phase in the subcortical deep gray matter of patients with clinically isolated syndrome may precede structure-specific atrophy.

BACKGROUND AND PURPOSE: Increasing evidence suggests that iron deposition is present in the later stages of MS. In this study we examined abnormal phase values, indicative of increased iron content on SWI-filtered phase images of the SDGM in CIS patients and HC. We also examined the association of abnormal phase with conventional MR imaging outcomes at first clinical onset. MATERIALS AND METHODS: Forty-two patients with CIS (31 female, 11 male) and 65 age and sex-matched HC (41 female, 24 male) were scanned on a 3T scanner. Mean age was 40.1 (SD = 10.4) years in patients with CIS, and 42.8 (SD = 14) years in HC, while mean disease duration was 1.2 years (SD = 1.3) in patients with CIS. MP-APT, NPTV, and normalized volume measurements were derived for all SDGM structures. Parametric and nonparametric group-wise comparisons were performed, and associations were determined with other MR imaging metrics. RESULTS: Patients with CIS had significantly increased MP-APT (P = .029) and MP-APT volume (P = .045) in the pulvinar nucleus of the thalamus compared with HC. Furthermore, the putamen (P = .004), caudate (P = .035), and total SDGM (P = .048) displayed significant increases in MP-APT volume, while MP-APT was also significantly increased in the putamen (P = .029). No global or regional volumetric MR imaging differences were found between the study groups. Significant correlations were observed between increased MP-APT volumes of total SDGM, caudate, thalamus, hippocampus, and substantia nigra with white matter atrophy and increased T2 lesion volume (P < .05). CONCLUSION: Patients with CIS showed significantly increased content and volume of iron, as determined by abnormal SWI-phase measurement, in the various SDGM structures, suggesting that iron deposition may precede structure-specific atrophy.

Cine cerebrospinal fluid imaging in multiple sclerosis

To investigate cerebrospinal fluid (CSF) dynamics in the aqueduct of Sylvius in multiple sclerosis (MS) patients and healthy controls (HC) using cine phase contrast imaging.

Changes of cine cerebrospinal fluid dynamics in patients with multiple sclerosis treated with percutaneous transluminal angioplasty: a case-control study.

PURPOSE To investigate characteristics of cine phase contrast-calculated cerebrospinal fluid (CSF) flow and velocity measures in patients with relapsing-remitting (RR) multiple sclerosis (MS) receiving standard medical treatment who had been diagnosed with chronic cerebrospinal venous insufficiency (CCSVI) and underwent percutaneous transluminal angioplasty (PTA). MATERIALS AND METHODS This case-controlled, magnetic resonance (MR) imaging-blinded study included 15 patients with RR MS who presented with significant stenoses (≥50% lumen reduction on catheter venography) in the azygous or internal jugular veins. Eight patients underwent PTA in addition to medical therapy immediately following baseline assessments (case group) and seven had delayed PTA after 6 months of medical therapy alone (control group). CSF flow and velocity measures were quantified over 32 phases of the cardiac cycle by a semiautomated method. Outcomes were compared between groups at baseline and at 6 and 12 months of the study by mixed-effect model analysis. RESULTS At baseline, no significant differences in CSF flow or velocity measures were detected between groups. At month 6, significant improvement in flow (P<.001) and velocity (P = .013) outcomes were detected in the immediate versus the delayed group, and persisted to month 12 (P = .001 and P = .021, respectively). Within-group flow comparisons from baseline to follow-up showed a significant increase in the immediate group (P = .033) but a decrease in the delayed group (P = .024). Altered CSF flow and velocity measures were associated with worsening of clinical and MR outcomes in the delayed group. CONCLUSIONS PTA in patients with MS with CCSVI increased CSF flow and decreased CSF velocity, which are indicative of improved venous parenchyma drainage.

Aqueductal cerebrospinal fluid pulsatility in healthy individuals is affected by impaired cerebral venous outflow

To investigate cerebrospinal fluid (CSF) dynamics in the aqueduct of Sylvius (AoS) in chronic cerebrospinal venous insufficiency (CCSVI)‐positive and ‐negative healthy individuals using cine phase contrast imaging.