A multicenter pilot study evaluating simplified central vein assessment for the diagnosis of multiple sclerosis.

BACKGROUND: The central vein sign (CVS) is a proposed magnetic resonance imaging (MRI) biomarker for multiple sclerosis (MS); the optimal method for abbreviated CVS scoring is not yet established. OBJECTIVE: The aim of this study was to evaluate the performance of a simplified approach to CVS assessment in a multicenter study of patients being evaluated for suspected MS. METHODS: Adults referred for possible MS to 10 sites were recruited. A post-Gd 3D T2*-weighted MRI sequence (FLAIR*) was obtained in each subject. Trained raters at each site identified up to six CVS-positive lesions per FLAIR* scan. Diagnostic performance of CVS was evaluated for a diagnosis of MS which had been confirmed using the 2017 McDonald criteria at thresholds including three positive lesions (Select-3*) and six positive lesions (Select-6*). Inter-rater reliability assessments were performed. RESULTS: Overall, 78 participants were analyzed; 37 (47%) were diagnosed with MS, and 41 (53%) were not. The mean age of participants was 45 (range: 19-64) years, and most were female (n = 55, 71%). The area under the receiver operating characteristic curve (AUROC) for the simplified counting method was 0.83 (95% CI: 0.73-0.93). Select-3* and Select-6* had sensitivity of 81% and 65% and specificity of 68% and 98%, respectively. Inter-rater agreement was 78% for Select-3* and 83% for Select-6*. CONCLUSION: A simplified method for CVS assessment in patients referred for suspected MS demonstrated good diagnostic performance and inter-rater agreement.

Effect of GBCA Use on Detection and Diagnostic Performance of the Central Vein Sign: Evaluation Using a 3-T FLAIR* Sequence in Patients With Suspected Multiple Sclerosis.

BACKGROUND. The central vein sign (CVS) is a proposed MRI biomarker of multiple sclerosis (MS). The impact of gadolinium-based contrast agent (GBCA) administration on CVS evaluation remains poorly investigated. OBJECTIVE. The purpose of this study was to assess the effect of GBCA use on CVS detection and on the diagnostic performance of the CVS for MS using a 3-T FLAIR* sequence. METHODS. This study was a secondary analysis of data from the pilot study for the prospective multicenter Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis (CAVS-MS), which recruited adults with suspected MS from April 2018 to February 2020. Participants underwent 3-T brain MRI including FLAIR and precontrast and post-contrast echo-planar imaging T2*-weighted acquisitions. Postprocessing was used to generate combined FLAIR and T2*-weighted images (hereafter, FLAIR*). MS diagnoses were established using the 2017 McDonald criteria. Thirty participants (23 women, seven men; mean age, 45 years) were randomly selected from the CAVS-MS pilot study cohort. White matter lesions (WMLs) were marked using FLAIR* images. A single observer, blinded to clinical data and GBCA use, reviewed marked WMLs on FLAIR* images for the presence of the CVS. RESULTS. Thirteen of 30 participants had MS. Across participants, on precontrast FLAIR* imaging, 218 CVS-positive and 517 CVS-negative WMLs were identified; on post-contrast FLAIR* imaging, 269 CVS-positive and 459 CVS-negative WMLs were identified. The fraction of WMLs that were CVS-positive on precontrast and postcontrast images was 48% and 58% in participants with MS and 7% and 10% in participants without MS, respectively. The median patient-level CVS-positivity rate on precontrast and postcontrast images was 43% and 67% for participants with MS and 4% and 8% for participants without MS, respectively. In a binomial model adjusting for MS diagnoses, GBCA use was associated with an increased likelihood of at least one CVS-positive WML (odds ratio, 1.6; p < .001). At a 40% CVS-positivity threshold, the sensitivity of the CVS for MS increased from 62% on precontrast images to 92% on postcontrast images (p = .046). Specificity was not significantly different between precontrast (88%) and postcontrast (82%) images (p = .32). CONCLUSION. GBCA use increased CVS detection on FLAIR* images, thereby increasing the sensitivity of the CVS for MS diagnoses. CLINICAL IMPACT. The postcontrast FLAIR* sequence should be considered for CVS evaluation in future investigational trials and clinical practice.

Evaluation of multi-echo ICA denoising for task based fMRI studies: Block designs, rapid event-related designs, and cardiac-gated fMRI.

Multi-echo fMRI, particularly the multi-echo independent component analysis (ME-ICA) algorithm, has previously proven useful for increasing the sensitivity and reducing false positives for functional MRI (fMRI) based resting state connectivity studies. Less is known about its efficacy for task-based fMRI, especially at the single subject level. This work, which focuses exclusively on individual subject results, compares ME-ICA to single-echo fMRI and a voxel-wise T2(⁎) weighted combination of multi-echo data for task-based fMRI under the following scenarios: cardiac-gated block designs, constant repetition time (TR) block designs, and constant TR rapid event-related designs. Performance is evaluated primarily in terms of sensitivity (i.e., activation extent, activation magnitude, percent detected trials and effect size estimates) using five different tasks expected to evoke neuronal activity in a distributed set of regions. The ME-ICA algorithm significantly outperformed all other evaluated processing alternatives in all scenarios. Largest improvements were observed for the cardiac-gated dataset, where ME-ICA was able to reliably detect and remove non-neural T1 signal fluctuations caused by non-constant repetition times. Although ME-ICA also outperformed the other options in terms of percent detection of individual trials for rapid event-related experiments, only 46% of all events were detected after ME-ICA; suggesting additional improvements in sensitivity are required to reliably detect individual short event occurrences. We conclude the manuscript with a detailed evaluation of ME-ICA outcomes and a discussion of how the ME-ICA algorithm could be further improved. Overall, our results suggest that ME-ICA constitutes a versatile, powerful approach for advanced denoising of task-based fMRI, not just resting-state data.

Imaging left ventricular tissue mechanics and hemodynamics during supine bicycle exercise using a combined tagging and phase-contrast MRI pulse sequence.

Imaging the left ventricular mechanical and hemodynamic response to the stress of exercise may offer early prognosis in select patients with cardiac disease. Here, we demonstrate the feasibility of obtaining simultaneous measurements of longitudinal strain and transvalvular blood velocity during supine bicycle exercise stress in a wide bore magnetic resonance scanner. Combining information from the two datasets, we observe that although the time to peak strain (33.28 ± 1.86 versus 25.7 ± 2.12 as % of R-R interval) and time to peak mitral inflow velocity (44.37 ± 5.21 versus 35.5 ± 4.19 as % of R-R interval) from R-wave of the QRS complex occurred earlier during stress, the time from peak strain to peak mitral inflow velocity was not statistically different (16.5 ± 3.23 versus 13.4 ± 3.06). Further, the percentage of longitudinal relaxation at peak mitral inflow velocity was higher during stress (63.5 ± 7.72 versus 84.32 ± 6.24). These results suggest that although diastole is shortened, early diastolic filling efficiency is augmented during exercise stress in normal volunteers in an effort to maintain stroke volume.

Prospective head-movement correction for high-resolution MRI using an in-bore optical tracking system.

In MRI of the human brain, subject motion is a major cause of magnetic resonance image quality degradation. To compensate for the effects of head motion during data acquisition, an in-bore optical motion tracking system is proposed. The system comprises two MR-compatible infrared cameras that are fixed on a holder right above and in front of the head coil. The resulting close proximity of the cameras to the object allows precise tracking of its movement. During image acquisition, the MRI scanner uses this tracking information to prospectively compensate for head motion by adjusting the gradient field direction and radio frequency (RF) phases and frequencies. Experiments performed on subjects demonstrate robust system performance with translation and rotation accuracies of 0.1 mm and 0.15 degrees, respectively.

Real time high spatial-temporal resolution flow imaging with spiral MRI using auto-calibrated SENSE.

A novel spiral phase contrast technique was developed for high temporal and spatial resolution imaging of blood flow without cardiac gating. Spiral sampling of k-space has excellent flow properties and acquisition speed. Parallel imaging using the coil sensitivity maps can be used to reduce the imaging duration at the cost of SNR. An auto-calibrated spiral sensitivity encoding method is introduced and used for reconstruction of phase contrast images. Phase estimation for a simulated phantom using data from various acceleration rates was compared to the true phase map. To study the accuracy of the flow estimate with parallel image reconstruction, a high resolution cardiac gated experiment was performed and a subset of under-sampled data were reconstructed. The real-time experiments were performed to measure blood velocity in the ascending aorta and through the aortic valve with high spatial and temporal resolution. Temporal resolution of the flow images was improved by a factor of at least three with no cardiac gating signal with preserved spatial resolution. The results demonstrate the potential of using the technique for real-time flow imaging with improved spatial and temporal resolution.

Quantitative ischemia detection during cardiac magnetic resonance stress testing by use of FastHARP.

BACKGROUND: Because ECG alterations caused by ischemia cannot be reliably detected in the high-field MRI environment, detection of wall motion abnormalities is often used to ensure patient safety during stress testing. However, an experienced observer is needed to detect these abnormalities. In this study, we investigate the use of fast harmonic phase (FastHARP) MRI for the quantitative, operator-independent detection of the onset of ischemia during acute coronary occlusion. METHODS AND RESULTS: Eight mongrel dogs underwent an acute 2-minute closed-chest coronary artery occlusion while continuous FastHARP images were acquired. Full regional wall strain was determined every other heartbeat in a single short-axis imaging slice. After 5 minutes of reperfusion, a second 2-minute ischemic episode was induced during the acquisition of conventional cine wall-motion images. The time at which ECG alterations were observed during the first ischemic period was recorded. The time from occlusion to the detection of ischemia, based on a consensus of 2 blinded observers, was determined for MRI. No significant ischemia was present in 2 animals. In the remaining animals, the onset of ischemia was detected significantly earlier by FastHARP than by cine MRI (9.5+/-5 versus 33+/-14 seconds, P<0.01). HARP ischemia detection preceded ECG changes, on average, by 54 seconds. CONCLUSIONS: The rapid acquisition and detection of induced ischemia with FastHARP MRI shows promise as a nonsubjective method to diagnose significant coronary lesions during MR stress testing.