Christopher Nguyen

In vivo three‐dimensional high resolution cardiac diffusion‐weighted MRI: A motion compensated diffusion‐prepared balanced steady‐state free precession approach

The aim of this study was to implement and optimize a novel application of diffusion‐prepared balanced steady‐state free precession (bSSFP) to perform in vivo cardiac diffusion‐weighted MRI.

In vivo contrast free chronic myocardial infarction characterization using diffusion-weighted cardiovascular magnetic resonance

BackgroundDespite the established role of late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in characterizing chronic myocardial infarction (MI), a significant portion of chronic MI patients are contraindicative for the use of contrast agents. One promising alternative contrast free technique is diffusion weighted CMR (dwCMR), which has been shown ex vivo to be sensitive to myocardial fibrosis. We used a recently developed in vivo dwCMR in chronic MI pigs to compare apparent diffusion coefficient (ADC) maps with LGE imaging for infarct characterization.MethodsIn eleven mini pigs, chronic MI was induced by complete occlusion of the left anterior descending artery for 150 minutes. LGE, cine, and dwCMR imaging was performed 8 weeks post MI. ADC maps were derived from three orthogonal diffusion directions (b = 400 s/mm2) and one non-diffusion weighted image. Two semi-automatic infarct classification methods, threshold and full width half max (FWHM), were performed in both LGE and ADC maps. Regional wall motion (RWM) analysis was performed and compared to ADC maps to determine if any observed ADC change was significantly influenced by bulk motion.ResultsADC of chronic MI territories was significantly increased (threshold: 2.4 ± 0.3 μm2/ms, FWHM: 2.4 ± 0.2 μm2/ms) compared to remote myocardium (1.4 ± 0.3 μm2/ms). RWM was significantly reduced (threshold: 1.0 ± 0.4 mm, FWHM: 0.9 ± 0.4 mm) in infarcted regions delineated by ADC compared to remote myocardium (8.3 ± 0.1 mm). ADC-derived infarct volume and location had excellent agreement with LGE. Both LGE and ADC were in complete agreement when identifying transmural infarcts. Additionally, ADC was able to detect LGE-delineated infarcted segments with high sensitivity, specificity, PPV, and NPV. (threshold: 0.88, 0.93, 0.87, and 0.94, FWHM: 0.98, 0.97, 0.93, and 0.99, respectively).ConclusionsIn vivo diffusion weighted CMR has potential as a contrast free alternative for LGE in characterizing chronic MI.

Multiparametric magnetic resonance imaging localizes established extracapsular extension of prostate cancer

OBJECTIVE To define the accuracy of multiparametric magnetic resonance imaging (MP-MRI) for identifying focal and established extracapsular extension (ECE) in various zones of the prostate. METHODS Between 2010 and 2013, 342 patients underwent MP-MRI of the prostate (3T, no endorectal coil with axial perfusion and diffusion images). The findings of the images were reported as negative, suspicious, or positive for ECE by a single expert radiologist. Radical prostatectomy specimens were reviewed to confirm the size and the location of ECE and further defined as focal or established ECE. Established ECE included extension that was multifocal or involving more than 5 glands. The accuracy of MRI in localizing focal and established ECE to each zone of the prostate was determined. Regression analyses were performed to identify predictors of ECE. RESULTS We identified 112 patients who underwent prostate MP-MRI and radical prostatectomy. MRI findings considered suspicious or definite for ECE accurately predicted pathologic ECE (P<0.001). MP-MRI identified established ECE but not focal ECE. Sensitivity, specificity, positive predictive value, and negative predictive value of MP-MRI for established ECE were 70.7%, 90.6%, 57.1%, and 95.1%, respectively. MRI identified ECE to the left vs. right side as well as each zone of the prostate; however, sensitivity was lowest at the apex. On multivariate analysis, MRI was a significant predictor of ECE that was independent of prostate-specific antigen level, Gleason score, and clinical stage. CONCLUSION MP-MRI is useful for identifying established but not focal ECE in all zones of the prostate. MRI was a significant independent predictor of established ECE and may be a useful adjunct in staging prostate cancer.

Three-Dimensional Structure of the Human Myeloma IgG2

Human immunoglobulin G, subclass 2 (hIgG2), plays an important role in immunity to bacterial pathogens and in numerous pathological conditions. However, there is a lack of information regarding the three-dimensional (3D) structure of the hIgG2 molecule. We used electron microscopy (EM), differential scanning microcalorimetry (DSC) and fluorescence for structural analysis of the hIgG2. DSC and fluorescence indicated two types of interaction between CH1 domain of Fab (antigen-binding fragment/subunit) and CH2 domain of Fc (complement fixation fragment/subunit) simultaneously present in the sample: close interaction, which increases the thermostability of both, CH1 and CH2 domains, and weak (or no) interaction, which is typical for most IgGs but not hIgG2. Thermodynamics could not determine if both types of interactions are present within a single molecule. To address this question, EM was used. We employed a single-particle reconstruction and negative staining approach to reveal the three-dimensional structure of the hIgG2. A three-dimensional model of hIgG2 was created at 1.78 nm resolution. The hIgG2 is asymmetrical: one Fab subunit is in close proximity to the upper portion of the Fc subunit (CH2 domain) and the other Fab is distant from Fc. The plane of Fab subunits is nearly perpendicular to Fc. EM structure of the hIgG2 is in good agreement with thermodynamic data: a Fab distant from Fc should exhibit a lower melting temperature while a Fab interacting with Fc should exhibit a higher melting temperature. Both types of Fab subunits exist within one molecule resembling an A/B hIgG2 isoform introduced earlier on physicochemical level by Dillon et al. (2008). In such an arrangement, the access to the upper portion of Fc subunit is partially blocked by a Fab subunit. That might explain for instance why hIgG2 mildly activates complement and binds poorly to Fc receptors. Understanding of the three-dimensional structure of the hIgG2 should lead to better design of antibody-based therapeutics.

Early Detection and Quantification of Cerebral Venous Thrombosis by Magnetic Resonance Black-Blood Thrombus Imaging

Background and Purpose— Early diagnosis of cerebral venous thrombosis (CVT) is currently a major clinical challenge. We proposed a novel magnetic resonance black-blood thrombus imaging technique (MRBTI) for detection and quantification of CVT. Methods— MRBTI was performed on 23 patients with proven CVT and 24 patients with negative CVT confirmed by conventional imaging techniques. Patients were divided into 2 groups based on the duration of clinical onset: ⩽7 days (group 1) and between 7 and 30 days (group 2). Signal/noise ratio was calculated for the detected thrombus, and contrast/noise ratio was measured between thrombus and lumen and also between thrombus and brain tissue. The feasibility of using MRBTI for thrombus volume measurement was explored, and total thrombus volume was calculated for each patient. Results— In 23 patients with proven CVT, MRBTI correctly identified 113 of 116 segments with a sensitivity of 97.4%. Thrombus signal/noise ratio was 153±57 and 261±95 for group 1 (n=10) and group 2 (n=13), respectively (P<0.01). Thrombus to lumen contrast/noise ratio was 149±57 and 256±94 for group 1 and group 2, respectively. Thrombus to brain tissue contrast/noise ratio was 41±36 and 120±63 (P<0.01), respectively. Quantification of thrombus volume was successfully conducted in all patients with CVT, and mean volume of thrombus was 10.5±6.9 mL. Conclusions— The current findings support that with effectively suppressed blood signal, MRBTI allows selective visualization of thrombus as opposed to indirect detection of venous flow perturbation and can be used as a promising first-line diagnostic imaging tool.

In vivo diffusion-tensor MRI of the human heart on a 3 tesla clinical scanner: An optimized second order (M2) motion compensated diffusion-preparation approach.

To optimize a diffusion‐prepared balanced steady‐state free precession cardiac MRI (CMR) technique to perform diffusion‐tensor CMR (DT‐CMR) in humans on a 3 Tesla clinical scanner

3D high-resolution diffusion-weighted MRI at 3T: Preliminary application in prostate cancer patients undergoing active surveillance protocol for low-risk prostate cancer

To improve spatial resolution and image quality of diffusion‐weighted (DW) MRI in detecting low‐risk prostate cancer (lrPC) in patients undergoing active surveillance protocol (AS‐PC), we propose the application of a diffusion‐prepared balanced steady‐state free precession (bSSFP) technique capable of multishot acquisition.

DANTE-prepared three-dimensional FLASH: A fast isotropic-resolution MR approach to morphological evaluation of the peripheral arterial wall at 3 Tesla.

To develop and assess a sequence using DANTE dark‐blood preparation combined with FLASH readout (DANTE‐FLASH) for rapid isotropic‐resolution three‐dimensional (3D) peripheral vessel wall imaging at 3 Tesla (T).

Prospective Pilot Trial to Evaluate a High Resolution Diffusion-Weighted MRI in Prostate Cancer Patients

Objectives High-resolution prostate imaging may allow for detection of subtle changes in tumor size, decrease the reliance on biopsies, and help define tumor boundaries during ablation. This pilot clinical trial evaluates a novel high-resolution prostate MRI for detection of small, biopsy-proven prostate tumors. Methods Our team developed a software that can be loaded on any modern MRI to generate high resolution diffusion-weighted imaging sequences (HR-DWI), which were compared to standard diffusion-weighted imaging sequence (S-DWI) in a prospective pilot trial in active surveillance patients. HR-DWI captures the entire volume of the prostate rather than sections, reducing streaking artifacts and geometric distortions. Multiple shots, rather than single shots, are used to differentiate signal and noise, enhancing resolution. All images were read by two radiologists. The primary outcome was the percent of biopsy-proven zones seen in 17 patients. The trial was powered to detect discordant proportions of 0.04 and 0.40 at one-sided alpha = 0.05. Results The resolution was defined using standard phantoms. HR-DWI produced a 5-fold improvement in spatial resolution when compared to S-DWI. Multiparametric (MP)-MRI incorporating S-DWI was useful for predicting biopsy results (AUC 0.72, Fishers exact p < 0.001); however, using HR-DWI allowed MP-MRI to be more highly predictive of biopsy results (AUC 0.88, Fishers exact p < 0.001). AUC for MP-MRI incorporating HR-DWI was significantly larger than MP-MRI incorporating S-DWI (p = 0.002). MP-MRI with HR-DWI had a sensitivity of 95.7% and identified tumor in 22 of 23 zones proven to have cancer on biopsy. In contrast, MP-MRI with S-DWI had a sensitivity of 60.9% and only identified 14 of 23 biopsy-positive zones (p = 0.004). Conclusion We developed a novel DWI and evaluated its improved resolution in a clinical setting. This technology has many potential applications and should be evaluated in future clinical trials as a patient management tool.

Diffusion Tensor Cardiac Magnetic Resonance Reveals Exosomes From Cardiosphere-Derived Cells Preserve Myocardial Fiber Architecture After Myocardial Infarction

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