Background Three-dimensional, ECG-gated, time-resolved, three-directional, velocity-encoded phase-contrast MRI (4D flow MRI) has been applied extensively to measure blood velocity in great vessels but has been much less used in diseased carotid arteries. Carotid artery webs (CaW) are non-inflammatory intraluminal shelf-like projections into the internal carotid artery (ICA) bulb that are associated with complex flow and cryptogenic stroke. Purpose: Optimize 4D flow MRI for measuring the velocity field of complex flow in the carotid artery bifurcation model that contains a CaW. Methods: A 3D printed phantom model created from computed tomography angiography (CTA) of a subject with CaW was placed in a pulsatile flow loop within the MRI scanner. 4D Flow MRI images of the phantom were acquired with five different spatial resolutions (0.50–2.00 mm3) and four different temporal resolutions (23–96 ms) and compared to a computational fluid dynamics (CFD) solution of the flow field as a reference. We examined four planes perpendicular to the vessel centerline, one in the common carotid artery (CCA) and three in the internal carotid artery (ICA) where complex flow was expected. At these four planes pixel-by-pixel velocity values, flow, and time average wall shear stress (TAWSS) were compared between 4D flow MRI and CFD. Hypothesis: An optimized 4D flow MRI protocol will provide a good correlation with CFD velocity and TAWSS values in areas of complex flow within a clinically feasible scan time (~ 10 min). Results: Spatial resolution affected the velocity values, time average flow, and TAWSS measurements. Qualitatively, a spatial resolution of 0.50 mm3 resulted in higher noise, while a lower spatial resolution of 1.50–2.00 mm3 did not adequately resolve the velocity profile. Isotropic spatial resolutions of 0.50–1.00 mm3 showed no significant difference in total flow compared to CFD. Pixel-by-pixel velocity correlation coefficients between 4D flow MRI and CFD were > 0.75 for 0.50–1.00 mm3 but were < 0.5 for 1.50 and 2.00 mm3. Regional TAWSS values determined from 4D flow MRI were generally lower than CFD and decreased at lower spatial resolutions (larger pixel sizes). TAWSS differences between 4D flow and CFD were not statistically significant at spatial resolutions of 0.50–1.00 mm3 but were different at 1.50 and 2.00 mm3. Differences in temporal resolution only affected the flow values when temporal resolution was > 48.4 ms; temporal resolution did not affect TAWSS values. Conclusion: A spatial resolution of 0.74–1.00 mm3 and a temporal resolution of 23–48 ms (1–2 k-space segments) provides a 4D flow MRI protocol capable of imaging velocity and TAWSS in regions of complex flow within the carotid bifurcation at a clinically acceptable scan time.

Purpose: Chiari malformation type I (CMI) patients have been independently shown to have both increased resistance to cerebrospinal fluid (CSF) flow in the cervical spinal canal and greater cardiac-induced neural tissue motion compared to healthy controls. The goal of this paper is to determine if a relationship exists between CSF flow resistance and brain tissue motion in CMI subjects. Methods: Computational fluid dynamics (CFD) techniques were employed to compute integrated longitudinal impedance (ILI) as a measure of unsteady resistance to CSF flow in the cervical spinal canal in thirty-two CMI subjects and eighteen healthy controls. Neural tissue motion during the cardiac cycle was assessed using displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) technique. Results: The results demonstrate a positive correlation between resistance to CSF flow and the maximum displacement of the cerebellum for CMI subjects (r = 0.75, p = 6.77 × 10−10) but not for healthy controls. No correlation was found between CSF flow resistance and maximum displacement in the brainstem for CMI or healthy subjects. The magnitude of resistance to CSF flow and maximum cardiac-induced brain tissue motion were not statistically different for CMI subjects with and without the presence of five CMI symptoms: imbalance, vertigo, swallowing difficulties, nausea or vomiting, and hoarseness. Conclusion: This study establishes a relationship between CSF flow resistance in the cervical spinal canal and cardiac-induced brain tissue motion in the cerebellum for CMI subjects. Further research is necessary to understand the importance of resistance and brain tissue motion in the symptomatology of CMI.

Dyssynchrony During Acute RV Apex Pacing. Introduction: Patients with heart block have conventionally received a pacemaker that stimulates the right ventricular apex (RVA) to restore heart rate control. While RVA pacing has been shown to create systolic dyssynchrony acutely, dyssynchrony can also occur in diastole. The effects of acute RVA pacing on diastolic synchrony have not been investigated. RVA pacing acutely impairs diastolic function by increasing the time constant of relaxation, decreasing the peak lengthening rate and decreasing peak negative dP/dt. We therefore hypothesized that acute RVA pacing would cause diastolic dyssynchrony in addition to creating systolic dyssynchrony. Methods and Results: Fourteen patients (13 ± 4 years old) with non-preexcited supraventricular tachycardia underwent ablation therapy with subsequent testing to confirm elimination of the tachycardia substrate. Normal cardiac structure and function were then documented on two-dimensional echocardiography and 12-lead electrocardiography prior to enrollment. Tissue Doppler images were collected during normal sinus rhythm (NSR), right atrial appendage pacing (AAI), and VVI-RVA pacing during the postablation waiting interval. Systolic and diastolic dyssynchrony were quantified using cross-correlation analysis of tissue Doppler velocity curves. Systolic dyssynchrony increased 81% during RVA pacing relative to AAI and NSR (P < 0.01). Diastolic synchrony was not affected by the different pacing modes (P = 0.375). Conclusion: Acute dyssynchronous activation of the LV created by RVA pacing resulted in systolic dyssynchrony with preserved diastolic synchrony in pediatric patients following catheter ablation for treatment of supraventricular tachycardia. Our results suggest that systolic and diastolic dyssynchrony are not tightly coupled and may develop through separate mechanisms.

Background Approximately 5% of patients with an acute coronary syndrome are discharged from the emergency room with an erroneous diagnosis of non-cardiac chest pain. Highly accurate non-invasive stress imaging is valuable for assessment of low-risk chest pain patients to prevent these errors. Adenosine stress cardiovascular magnetic resonance (AS-CMR) is an imaging modality with increasing application. The goal of this study was to evaluate the negative prognostic value of AS-CMR among low-risk acute chest pain patients. Methods We studied 103 patients, mean 56.7 ± 12.3 years of age, with chest pain and no electrocardiographic evidence of ischemia and negative cardiac biomarkers of necrosis, who were admitted to the Cardiac Decision Unit of our institution. All patients underwent AS-CMR. A negative AS-CMR was defined as absence of all the following: regional wall motion abnormalities at rest; perfusion defects during stress (adenosine) and rest; and myocardial scar on late gadolinium enhancement images. The patients were followed for a mean of 277 (range 161-462) days. The primary end point was defined as the combination of cardiac death, nonfatal acute myocardial infarction, re-hospitalization for chest pain, obstructive coronary artery disease (>50% coronary stenosis on invasive angiography) and coronary revascularization. Results In 14 patients (13.6%), AS-CMR was positive. The remaining 89 patients (86.4%), who had negative AS-CMR, were discharged. No patient with negative AS-CMR reached the primary end-point during follow-up. The negative predictive value of AS-CMR was 100%. Conclusion AS-CMR holds promise as a useful tool to rule out significant coronary artery disease in patients with low-risk chest pain. Patients with negative AS-CMR have an excellent short and mid-term prognosis.

BACKGROUND: Significant paravalvular leak (PVL) after transcatheter aortic valve replacement (TAVR) confers a worse prognosis. Symptoms related to significant PVL may be difficult to differentiate from those related to other causes of heart failure. Cardiovascular magnetic resonance (CMR) directly quantifies valvular regurgitation, but has not been extensively studied in symptomatic post-TAVR patients. METHODS: CMR was compared to qualitative (QE) and semi-quantitative echocardiography (SQE) for classifying PVL and prognostic value at one year post-imaging in 23 symptomatic post-TAVR patients. The primary outcome was a composite of all-cause death, heart failure hospitalization, and intractable symptoms necessitating repeat invasive therapy; the secondary outcome was a composite of all-cause death and heart failure hospitalization. The difference in event-free survival according to greater than mild PVL versus mild or less PVL by QE, SQE, and CMR were evaluated by Kaplan-Meier survival analysis. RESULTS: Compared to QE, CMR reclassified PVL severity in 48% of patients, with most patients (31%) reclassified to at least one grade higher. Compared to SQE, CMR reclassified PVL severity in 57% of patients, all being reclassified to at least one grade lower; SQE overestimated PVL severity (mean grade 2.5 versus 1.7, p=0.001). The primary and secondary outcomes occurred in 48% and 35% of patients, respectively. Greater than mild PVL by CMR was associated with reduced event-free survival for the primary outcome (p<0.0001), however greater than mild PVL by QE and SQE were not (p=0.83 and p=0.068). Greater than mild PVL by CMR was associated with reduced event-free survival for the secondary outcome, as well (p=0.012). CONCLUSION: In symptomatic post-TAVR patients, CMR commonly reclassifies PVL grade compared with QE and SQE. CMR provides superior prognostic value compared to QE and SQE, as patients with greater than mild PVL by CMR (RF>20%) had a higher incidence of adverse events.

Background: To develop a technique to non-invasively estimate Stroke Volume (SV) in real-time during Magnetic Resonance Imaging (MRI) guided procedures, based on induced Magnetohydrodynamic Voltages (VMHD) that occur in Electrocardiogram (ECG) recordings during MRI exams, leaving the MRI scanner free to perform other imaging tasks. Due to the relationship between blood-flow (BF) and VMHD, we hypothesized that a method to obtain SV could be derived from extracted VMHD vectors in the Vectorcardiogram frame-of-reference (VMHDVCG). Methods and Results: To estimate a subject-specific BF-VMHD model, VMHDVCG was acquired during a 20-second breath-hold and calibrated versus aortic BF measured using Phase Contrast Magnetic Resonance (PCMR) in 10 subjects (n=10) and one subject diagnosed with Premature Ventricular Contractions (PVCs). Beat-to-Beat validation of VMHDVCG derived BF was performed using Real-Time Phase Contrast (RTPC) imaging in 7 healthy subjects (n=7) during a 15 minute cardiac exercise stress tests and 30 minutes after stress relaxation in 3T MRIs. Subject-specific equations were derived to correlate VMHDVCG to BF at rest, and validated using RTPC. An average error of 7.22% and 3.69% in SV estimation, respectively, was found during peak stress, and after complete relaxation. Measured beat-to-beat blood flow time-history derived from RTPC and VMHD were highly correlated using a Spearman Rank Correlation Coefficient during stress tests (0.89) and after stress relaxation (=0.86). Conclusions: Accurate beat-to-beat SV and BF were estimated using VMHDVCG extracted from intra-MRI 12-lead ECGs, providing a means to enhance patient monitoring during MR imaging and MR-guided interventions.

We report on the diagnostic capability of magnetic resonance imaging (MRI)-based tracking of ferumoxytol-labeled human neural progenitor cells (hNPCs) transplanted into the porcine spinal cord. hNPCs prelabeled with two doses of ferumoxytol nanoparticles (hNPC-F Low and hNPC-F High ) were injected into the ventral horn of the spinal cord in healthy minipigs. Ferumoxytol-labeled grafts were tracked in vivo up to 105 days after transplantation with MRI. Injection accuracy was assessed in vivo at day 14 and was predictive of “on” or “off” target cell graft location assessed by histology. No difference in long-term cell survival, assessed by quantitative stereology, was observed among hNPCF Low , hNPC-F High , or control grafts. Histological iron colocalized with MRI signal and engrafted human nuclei. Furthermore, the ferumoxytol-labeled cells retained nanoparticles and function in vivo. This approach represents an important leap forward toward facilitating translation of cell-tracking technologies to clinical trials by providing a method of assessing transplantation accuracy, delivered dose, and potentially cell survival.

Central nervous system (CNS) tissue motion of the brain occurs over 30 million cardiac cycles per year due to intracranial pressure differences caused by the pulsatile blood flow and cerebrospinal fluid (CSF) motion within the intracranial space. This motion has been found to be elevated in type 1 Chiari malformation. The impact of CNS tissue motion on CSF dynamics was assessed using a moving-boundary computational fluid dynamics (CFD) model of the cervical-medullary junction (CMJ). The cerebellar tonsils and spinal cord were modeled as rigid surfaces moving in the caudocranial direction over the cardiac cycle. The CFD boundary conditions were based on in vivo MR imaging of a 35-year old female Chiari malformation patient with ~150–300 µm motion of the cerebellar tonsils and spinal cord, respectively. Results showed that tissue motion increased CSF pressure dissociation across the CMJ and peak velocities up to 120 and 60%, respectively. Alterations in CSF dynamics were most pronounced near the CMJ and during peak tonsillar velocity. These results show a small CNS tissue motion at the CMJ can alter CSF dynamics for a portion of the cardiac cycle and demonstrate the utility of CFD modeling coupled with MR imaging to help understand CSF dynamics.