Quantitative myocardial perfusion in mice based on the signal intensity of flow sensitized CMR.

BACKGROUND: In the conventional approach to arterial spin labeling in the rodent heart, the relative difference in the apparent T(1) relaxation times corresponding to selective and non-selective inversion is related to perfusion via a two compartment model of tissue. But accurate determination of T(1) in small animal hearts is difficult and prone to errors due to long scan times and high heart rates. In this study we introduce the theoretical frame work for an alternative method (SI-method) based purely on the signal intensity of slice-select and non-select inversion recovery images at a single inversion time at short repetition time. METHODS: A modified Bloch equation was solved to derive perfusion as a function of signal intensity of flow sensitized segmented gradient echo acquisitions. A two compartment fast exchanging model of tissue was assumed. To test the new technique first it was implemented on a flow phantom and then it was compared with the conventional T(1) method in an in vivo study of healthy C57BL/6 mice (n=12). Finally the SI-method was used in comparison to a Late Gadolinium Enhanced (LGE) method to qualitatively and quantitatively assess perfusion deficits in an ischemia-reperfusion mouse model (n=4). RESULTS: The myocardial perfusion of healthy mice obtained by the SI-method, 5.6 ± 0.5 ml/g/min, (mean ± standard deviation) was similar (p=0.38) to that obtained by the conventional method, 5.6 ± 0.3 ml/g/min. The variance in perfusion within the left ventricle was less for the SI-method than that for the conventional method (p<0.0001). The mean percentage standard deviation among repeated measures was 3.6%. The LGE regions of the ischemia reperfusion model were matched with regions of hypo-perfusion in the perfusion map. The average perfusion in the hypo perfused region among all four IR mice was 1.2 ± 0.9 ml/g/min and that of the remote region was 4.4 ± 1.2 ml/g/min. CONCLUSIONS: The proposed signal intensity based ASL method with a segmented acquisition scheme allows accurate high resolution perfusion mapping in small animals. It's short scan time, high reproducibility and ease of post process makes it a robust alternative to the conventional ASL technique that relies on T(1) measurements.

Presence of mechanical dyssynchrony in Duchenne muscular dystrophy.

BACKGROUND: Cardiac dysfunction in boys with Duchenne muscular dystrophy (DMD) is a leading cause of death. Cardiac resynchronization therapy (CRT) has been shown to dramatically decrease mortality in eligible adult population with congestive heart failure. We hypothesized that mechanical dyssynchrony is present in DMD patients and that cardiovascular magnetic resonance (CMR) may predict CRT efficacy. METHODS: DMD patients (n = 236) were stratified into 4 groups based on age, diagnosis of DMD, left ventricular (LV) ejection fraction (EF), and presence of myocardial fibrosis defined as positive late gadolinum enhancement (LGE) compared to normal controls (n = 77). Dyssynchrony indices were calculated based on timing of CMR derived circumferential strain (ecc). The calculated indices included cross-correlation delay (XCD), uniformity of strain (US), regional vector of variance (RVV), time to maximum strain (TTMS) and standard deviation (SD) of TTMS. Abnormal XCD value was defined as > normal + 2SD. US, RVV, TTMS and SD were calculated for patients with abnormal XCD. RESULTS: There was overall low prevalence of circumferential dyssynchrony in the entire DMD population; it increased to 17.1% for patients with abnormal EF and to 31.2% in the most advanced stage (abnormal EF with fibrosis). All but one DMD patient with mechanical dyssynchrony exhibited normal QRS duration suggesting absence of electrical dyssynchrony. The calculated US and RVV values (0.91 ± 0.09, 1.34 ± 0.48) indicate disperse rather than clustered dyssynchrony. CONCLUSION: Mechanical dyssynchrony is frequent in boys with end stage DMD-associated cardiac dysfunction. It is associated with normal QRS complex as well as extensive lateral fibrosis. Based on these findings, it is unlikely that this patient population will benefit from CRT.

Left ventricular T2 distribution in Duchenne muscular dystrophy.

BACKGROUND: Although previous studies have helped define the natural history of Duchenne muscular dystrophy (DMD)-associated cardiomyopathy, the myocardial pathobiology associated with functional impairment in DMD is not yet known.The objective of this study was to assess the distribution of transverse relaxation time (T2) in the left ventricle (LV) of DMD patients, and to determine the association of myocardial T2 heterogeneity to the severity of cardiac dysfunction. DMD patients (n = 26) and normal control subjects (n = 13) were studied by cardiovascular magnetic resonance (CMR). DMD subject data was stratified based on subject age and LV ejection fraction (EF) into the following groups: A (<12 years old, n = 12); B (>or=12 years old, EF or=12 years old, EF = 55%, n = 6). Controls were also stratified by age into Groups N1 (<12 years, n = 6) and N2 (>12 years, n = 5). LV mid-slice circumferential myocardial strain (epsilon cc) was calculated using tagged CMR imaging. T2 maps of the LV were generated for all subjects using a black blood dual spin echo method at two echo times. The full width at half maximum (FWHM) was calculated from a histogram of LV T2 distribution constructed for each subject. RESULTS: In DMD subject groups, FWHM of the T2 histogram rose progressively with age and decreasing EF (Group A FWHM= 25.3 +/- 3.8 ms; Group B FWHM= 30.9 +/- 5.3 ms; Group C FWHM= 33.0 +/- 6.4 ms). Further, FWHM was significantly higher in those with reduced circumferential strain (|epsilon cc| 12% (Group A). Group A FWHM was not different from the two normal groups (N1 FWHM = 25.3 +/- 3.5 ms; N2 FWHM= 24.0 +/- 7.3 ms). CONCLUSION: Reduced EF and epsilon cc correlates well with increased T2 heterogeneity quantified by FWHM, indicating that subclinical functional impairments could be associated with pre-existing abnormalities in tissue structure in young DMD patients.

A novel ultrasound technique to detect early chronic kidney disease.

Chronic kidney disease (CKD) of unknown etiology is recognized as a major public health challenge and a leading cause of morbidity and mortality in the dry zone in Sri Lanka. CKD is asymptomatic and are diagnosed only in late stages. Evidence points to strong correlation between progression of CKD and kidney fibrosis. Several biochemical markers of renal fibrosis have been associated with progression of CKD. However, no marker is able to predict CKD consistently and accurately before being detected with traditional clinical tests (serum creatinine, and cystatin C, urine albumin or protein, and ultrasound scanning). In this paper, we hypothesize that fibrosis in the kidney, and therefore the severity of the disease, is reflected in the frequency spectrum of the scattered ultrasound from the kidney. We present a design of a simple ultrasound system, and a set of clinical and laboratory studies to identify spectral characteristics of the scattered ultrasound wave from the kidney that correlates with CKD. We believe that spectral parameters identified in these studies can be used to detect and stratify CKD at an earlier stage than what is possible with current markers of CKD.

In vivo MR thermometry of frozen tissue using R2* and signal intensity.

Cryoablation is one of several minimally invasive treatments that may be suitable for a targeted treatment of prostate cancer. Because efficacy is improved when a sufficiently cold end temperature is reached, the purpose of this work was to demonstrate an image-based thermometry method that could provide temperature maps throughout the frozen tissue. In five in vivo canine prostate cryoablation experiments performed under magnetic resonance imaging guidance, two MR parameters were measured and correlated to temperature: R2* and changes in signal intensity. R2* is elevated approximately linearly as tissue temperature decreases below the freezing point, while the signal intensity decreases exponentially. In vivo temperature maps with isotherms at -5 degrees C, -15 degrees C, and -30 degrees C are demonstrated.

Methodology for implementing patient-specific spatial boundary condition during a cardiac cycle from phase-contrast MRI for hemodynamic assessment.

Pulmonary insufficiency (PI) can render the right ventricle dysfunctional due to volume overloading and hypertrophy. The treatment requires a pulmonary valve replacement surgery. However, determining the right time for the valve replacement surgery has been difficult with currently employed clinical techniques such as, echocardiography and cardiac MRI. Therefore, there is a clinical need to improve the diagnosis of PI by using patient-specific (PS) hemodynamic endpoints. While there are many reported studies on the use of PS geometry with time varying boundary conditions (BC) for hemodynamic computation, few use spatially varying PS velocity measurement at each time point of the cardiac cycle. In other words, the gap is that, there are limited number of studies which implement both spatially- and time-varying physiologic BC directly with patient specific geometry. The uniqueness of this research is in the incorporation of spatially varying PS velocity data obtained from phase-contrast MRI (PC-MRI) at each time point of the cardiac cycle with PS geometry obtained from angiographic MRI. This methodology was applied to model the complex developing flow in human pulmonary artery (PA) distal to pulmonary valve, in a normal and a subject with PI. To validate the methodology, the flow rates from the proposed method were compared with those obtained using QFlow software, which is a standard of care clinical technique. For the normal subject, the computed time average flow rates from this study differed from those obtained using the standard of care technique (QFlow) by 0.8 ml/s (0.9%) at the main PA, by 2 ml/s (3.4%) at the left PA and by 1.4 ml/s (3.8%) at the right PA. For the subject with PI, the difference was 7 ml/s (12.4%) at the main PA, 5.5 ml/s (22.6%) at the left PA and 4.9 ml/s (18.0%) at the right PA. The higher percentage differences for the subject with PI, was the result of overall lower values of the forward mean flow rate caused by excessive flow regurgitation. This methodology is expected to provide improved computational results when PS geometry from angiographic MRI is used in conjunction with PS PC-MRI data for solving the flow field.

Asymmetric cell-matrix and biomechanical abnormalities in elastin insufficiency induced aortopathy.

Aortopathy is characterized by vascular smooth muscle cell (VSMC) abnormalities and elastic fiber fragmentation. Elastin insufficient (Eln (+/-)) mice demonstrate latent aortopathy similar to human disease. We hypothesized that aortopathy manifests primarily in the aorto-pulmonary septal (APS) side of the thoracic aorta due to asymmetric cardiac neural crest (CNC) distribution. Anatomic (aortic root vs. ascending aorta) and molecular (APS vs. non-APS) regions of proximal aorta tissue were examined in adult and aged wild type (WT) and mutant (Eln (+/-)) mice. CNC, VSMCs, elastic fiber architecture, proteoglycan expression, morphometrics and biomechanical properties were examined using histology, 3D reconstruction, micropipette aspiration and in vivo magnetic resonance imaging (MRI). In the APS side of Eln (+/-) aorta, Sonic Hedgehog (SHH) is decreased while SM22 is increased. Elastic fiber architecture abnormalities are present in the Eln (+/-) aortic root and APS ascending aorta, and biglycan is increased in the aortic root while aggrecan is increased in the APS aorta. The Eln (+/-) ascending aorta is stiffer than the aortic root, the APS side is thicker and stiffer than the non-APS side, and significant differences in the individual aortic root sinuses are observed. Asymmetric structure-function abnormalities implicate regional CNC dysregulation in the development and progression of aortopathy.

Patterns of left ventricular remodeling in patients with Duchenne Muscular Dystrophy: a cardiac MRI study of ventricular geometry, global function, and strain.

The cardiac disease ubiquitously associated in Duchenne Muscular Dystrophy (DMD) has traditionally been considered a progressive dilated cardiomyopathy (DCM). However, left ventricular (LV) dilatation as measured with cardiac MRI has not been a consistent finding in this population, even as circumferential strain (ε(cc)) declines with advancing disease. We hypothesized that a distinct pattern of changes in LV geometry, during the course of ε(cc) decline, distinguishes DMD associated heart disease from DCM. Using CMR, LV end-diastolic volume (EDV), mass (LVM), ejection fraction, ε(cc) and myocardial delayed enhancement (MDE) were determined in DMD patients and normal control subjects. The LV Remodeling Index (LVRI) was calculated as the ratio of LV Mass to Volume (LVM/EDV). Statistical comparisons between all LV parameters and genotype were also performed. Median LVRI in DMD (n = 127) and control subjects (n = 41) were different (0.75 vs. 0.65, P = 0.0150) but within normal range. Furthermore, the median LVRI in DMD boys with reduced LV systolic function was significantly reduced compared to those with normal LV systolic function (0.64 vs. 0.75, P = 0.0974). However, the presence of MDE was associated with a lower median LVRI (0.57 vs. 0.76, P = 0.0471). Regression analysis showed no significant correlation between ε(cc) and LVRI (r = -0.03). The LVRI of DMD patients is unexpectedly normal and not correlated with ε(cc.) Based on these findings, DMD-associated heart disease exhibits a unique remodeling pattern distinct from DCM.

Magnetic resonance imaging assessment of cardiac dysfunction in δ-sarcoglycan null mice.

Delta-sarcoglycan (δ-sarcoglycan) null, Scgd(-/-), mice develop cardiac and skeletal muscle histopathological alterations similar to those in humans with limb-girdle muscular dystrophy. The objective of this study was to assess the feasibility of using MRI to investigate cardiac dysfunction in Scgd(-/-) mice. Cardiac MRI of 8 month old Scgd(-/-) and wild type (WT) mice was performed. Compared to WT, Scgd(-/-) mice had significantly lower LV ejection fraction (44±5% vs. 66±4%, p=0.014), lower RV ejection fraction (25±2% vs. 51±3%, p<0.001) lower myocardial circumferential strain, (15.0±0.3% vs. 16.9±0.3%, p=0.007) and RV dilatation (54±3 µL vs. 40±3 µL, p=0.007). The regional circumferential strain also demonstrated significant temporal dyssynchrony between opposing regions of the Scgd(-/-) LV. Our results demonstrate severe cardiac dysfunction in Scgd(-/-) mice at 8 months. The study identifies a set of non-invasive markers that could be used to study efficacy of novel therapeutic agents in dystrophic mice.

Abdominal fat-water separation with SSFP at 3 Tesla.

The ability of the phase-sensitive steady-state free precession (SSFP) technique to distinguish subcutaneous and visceral adipose tissue in the abdomen at 3 T was evaluated. A phased array receiver radiofrequency coil and a commercially available SSFP sequence were used for imaging. The raw image data were postprocessed to generate fat-only and water-only images. A postprocessing algorithm that is computationally efficient and robust is presented. The postprocessing technique separates the fat and water pixels automatically without any user interference. The feasibility of the technique is demonstrated in vivo with breath-hold abdomen images. The short scan time and the ease of use of this technique are well suited to the quantification of body fat distribution in children.

Study of laser ablation in the in vivo rabbit brain with MR thermometry.

PURPOSE: To investigate the peak temperature and thermal dose (T(43)) as tissue damage indicators for thermal therapy. MATERIALS AND METHODS: The proton resonant frequency (PRF) shift thermal coefficient was calibrated on six in vivo rabbit brains during interstitial laser ablation. The peak temperature and T(43) were correlated with the lesion boundary observed on T2-weighted spin-echo (SE) MRI at 4 hours post-heating in seven thermal lesions using direct MR measurement and analysis based on a binary discriminate model. RESULTS: The peak temperature and T(43) were 48.3 +/- 1.7 degrees C and 191 +/- 219 minutes, respectively, from the direct MR measurement. The values derived by the binary discriminate analysis were 47.8 +/- 2.2 degrees C and 28 +/- 41 minutes, respectively. CONCLUSION: Our results suggest that tissue damage in rabbit brain 4 hours after thermal ablation can be predicted reliably from a threshold temperature of approximately 48 degrees C.