CAROTID THREE-DIMENSIONAL ULTRASOUND: LONGITUDINAL MEASUREMENT AND CARDIAC-GATED ACQUISITION

Carotid atherosclerosis is the main cause of stroke - the fourth leading cause of death in Canada - and can be quantified by ultrasound measurements. Intima-media thickness (IMT), total plaque area (TPA) and 3-dimensional ultrasound vessel wall volume (3DUS VWV) were compared in a longitudinal study of 71 patients with diabetic nephropathy randomized to vitamin B or placebo. Only 3DUS VWV was sensitive to a difference in change between treatment groups. We developed and tested cardiac-gated 3DUS acquisition for use in younger subjects with compliant arteries; images were acquired from 400 ms after the start of the cardiac cycle to the beginning of the next cardiac cycle. In healthy volunteers and rheumatoid arthritis patients, change in area over the cardiac cycle was reduced to below that seen in moderate atherosclerosis patients. 3DUS VWV can measure change in atherosclerosis and can now be used in younger patients at risk of atherosclerosis in future studies

Magnetic Resonance Imaging of a Natural Killer Cell Therapy in a Mouse Model of Prostate Cancer

Purpose: This thesis uses magnetic resonance imaging (MRI) techniques to study natural killer (NK) cell therapy in a nude mouse model of prostate cancer. Cellular MRI, anatomical MRI and hyperpolarized 13C spectroscopy were used to study various aspects of the model. Methods: The cells used were KHYG-1 NK cells and PC-3M prostate cancer cells. Imaging was performed on a clinical 3T GE MR 750 scanner, using a high-performance gradient insert for acquisition with the balanced steady state free precession (bSSFP) sequence, and using the built-in gradients for 13C pyruvate spectroscopy. Pyruvate was hyperpolarized by dynamic nuclear polarization. Results: KHYG-1 were toxic to PC-3M in vitro and were successfully labeled with MoldayRhodamine, a superparamagnetic iron oxide nanoparticle (SPIO). A subcutaneous PC-3M tumour model was used to investigate tracking of KHYG-1 in vivo using the bSSFP sequence. Four days after administration, KHYG-1 accumulation in the tumours was detected by histology but not by MRI, although labeled KHYG-1 at high density were visible in MR images. The bSSFP sequence was then optimized for imaging the mouse prostate and the whole mouse body. Tumour development in an orthotopic prostate cancer model was characterized by MRI and histology for tumour growth, metastasis and tumour metabolism. Tumours were visible by MRI day 9 after injection. Using histology, metastasis was detected in the lymph nodes and spleen of the mice. Necrotic regions in the tumours were detected on day 22 by both anatomical imaging and pyruvate spectroscopy and were confirmed by histology. Conclusions: KHYG-1 cell therapy shows promise as a treatment of prostate cancer. A mouse model that developed lymph node metastases was characterized. Based on the accumulation of KHYG-1 in SC tumours 4 days after administration, and the consistent presence of MRI-visible tumours on day 9-13, a treatment time point of 9-13 days is proposed for future NK cell tracking experiments

Tracking Neural Progenitor Cell Migration in the Rodent Brain Using Magnetic Resonance Imaging

The study of neurogenesis and neural progenitor cells (NPCs) is important across the biomedical spectrum, from learning about normal brain development and studying disease to engineering new strategies in regenerative medicine. In adult mammals, NPCs proliferate in two main areas of the brain, the subventricular zone (SVZ) and the subgranular zone, and continue to migrate even after neurogenesis has ceased within the rest of the brain. In healthy animals, NPCs migrate along the rostral migratory stream (RMS) from the SVZ to the olfactory bulb, and in diseased animals, NPCs migrate toward lesions such as stroke and tumors. Here we review how MRI-based cell tracking using iron oxide particles can be used to monitor and quantify NPC migration in the intact rodent brain, in a serial and relatively non-invasive fashion. NPCs can either be labeled directly in situ by injecting particles into the lateral ventricle or RMS, where NPCs can take up particles, or cells can be harvested and labeled in vitro, then injected into the brain. For in situ labeling experiments, the particle type, injection site, and image analysis methods have been optimized and cell migration toward stroke and multiple sclerosis lesions has been investigated. Delivery of labeled exogenous NPCs has allowed imaging of cell migration toward more sites of neuropathology, which may enable new diagnostic and therapeutic opportunities for as-of-yet untreatable neurological diseases

Optimization of the Balanced Steady State Free Precession (bSSFP) Pulse Sequence for Magnetic Resonance Imaging of the Mouse Prostate at 3T

INTRODUCTION: MRI can be used to non-invasively monitor tumour growth and response to treatment in mouse models of prostate cancer, particularly for longitudinal studies of orthotopically-implanted models. We have optimized the balanced steady-state free precession (bSSFP) pulse sequence for mouse prostate imaging. METHODS: Phase cycling, excitations, flip angle and receiver bandwidth parameters were optimized for signal to noise ratio and contrast to noise ratio of the prostate. The optimized bSSFP sequence was compared to T1- and T2-weighted spin echo sequences. RESULTS: SNR and CNR increased with flip angle. As bandwidth increased, SNR, CNR and artifacts such as chemical shift decreased. The final optimized sequence was 4 PC, 2 NEX, FA 50°, BW ±62.5 kHz and took 14-26 minutes with 200 µm isotropic resolution. The SNR efficiency of the bSSFP images was higher than for T1WSE and T2WSE. CNR was highest for T1WSE, followed closely by bSSFP, with the T2WSE having the lowest CNR. With the bSSFP images the whole body and organs of interest including renal, iliac, inguinal and popliteal lymph nodes were visible. CONCLUSION: We were able to obtain fast, high-resolution, high CNR images of the healthy mouse prostate with an optimized bSSFP sequence

Effect of phase cycling and averaging on ex vivo prostate image quality.

<p>Cropped and enlarged sections of axial scans: A: 2 PC, 4 NEX, B: 4 PC, 2 NEX, C: 8 PC, 1 NEX. Black arrowheads indicate prostate, white arrowheads urethra, FP is the fat pad used for CNR measurements and LN are the inguinal lymph nodes. Scale bar is 1 cm. Axial scan, FOV 4×4 cm, 200 µm isotropic resolution, TR/TE = 3.9/2.0 ms, FA 30°, BW ±62.5 kHz, 20 minutes.</p

Comparison of in vivo axial views acquired with A: bSSFP, B: T1wSE and C: T2wSW.

<p>Black arrows indicate prostate, white arrows indicate urethra. Scale bar is 1 cm. bSSFP images acquired using optimized sequence with 3×3 cm FOV. Spin echo sequences acquired with axial orientation, FOV 3×3 cm, TR/TE = 600/25 ms (T1w), 2000/70 ms (T2w), 1 mm slice thickness, 128×128 matrix, 234 mm in-plane resolution, and 20 (T1w) and 17 (T2w) minutes acquisition time.</p

Sections of coronal view of mouse with prostate and lymph nodes identified.

<p>Tail is at left, head at right. White arrows indicate organs of interest as follows. A: popliteal lymph nodes; B: prostate; C: iliac lymph nodes; D: inguinal lymph nodes with lymph vessels visible; E: Renal lymph nodes. Scale bar is 0.5 cm. Coronal scan, FOV 6×3.3 cm, 200 µm isotropic resolution, TR/TE = 4.6/2.3 ms, BW ±62.5 kHz, FA 40°, 8 PC, 2 NEX, 26 minutes.</p

3 views of prostate from one in-vivo scan.

<p>A: axial, B: coronal, C: sagittal. White arrows indicate prostate. Scale bar is 0.5 cm. Axial scan, FOV 3×3 cm, 200 µm isotropic resolution, TR/TE = 4.6 ms/2.3 ms, 4 PC, 2 NEX, FA 50°, BW ±62.5 kHz, 14 minutes.</p

Understanding Heterogeneity and Permeability of Brain Metastases in Murine Models of HER2-Positive Breast Cancer Through Magnetic Resonance Imaging: Implications for Detection and Therapy

OBJECTIVES: Brain metastases due to breast cancer are increasing, and the prognosis is poor. Lack of effective therapy is attributed to heterogeneity of breast cancers and their resulting metastases, as well as impermeability of the blood–brain barrier (BBB), which hinders delivery of therapeutics to the brain. This work investigates three experimental models of HER2+ breast cancer brain metastasis to better understand the inherent heterogeneity of the disease. We use magnetic resonance imaging (MRI) to quantify brain metastatic growth and explore its relationship with BBB permeability. DESIGN: Brain metastases due to breast cancer cells (SUM190-BR3, JIMT-1-BR3, or MDA-MB-231-BR-HER2) were imaged at 3 T using balanced steady-state free precession and contrast-enhanced T1-weighted spin echo sequences. The histology and immunohistochemistry corresponding to MRI were also analyzed. RESULTS: There were differences in metastatic tumor appearance by MRI, histology, and immunohistochemistry (Ki67, CD31, CD105) across the three models. The mean volume of an MDA-MB-231-BR-HER2 tumor was significantly larger compared to other models (F2,12 = 5.845, P < .05); interestingly, this model also had a significantly higher proportion of Gd-impermeable tumors (F2,12 = 22.18, P < .0001). Ki67 staining indicated that Gd-impermeable tumors had significantly more proliferative nuclei compared to Gd-permeable tumors (t[24] = 2.389, P < .05) in the MDA-MB-231-BR-HER2 model. CD31 and CD105 staining suggested no difference in new vasculature patterns between permeable and impermeable tumors in any model. CONCLUSION: Significant heterogeneity is present in these models of brain metastases from HER2+ breast cancer. Understanding this heterogeneity, especially as it relates to BBB permeability, is important for improvement in brain metastasis detection and treatment delivery