MSBI Thesis & Abstracts 2011-2012

Wei-Ching Lo
Advisor: Dr. Xiaojuan Li, PhD
Thesis Title:  Advanced Image Analysis and Finite Element Modeling for Knees with Acute Injury
Abstract:
Articular cartilage plays an important role in the knee joint, which is the largest joint in the body and carries high loads. Injury to the anterior cruciate ligament (ACL) will affect the joint stability and lead to post–traumatic osteoarthritis development. Finite element (FE) models have been used to analyze cartilage deformation and kinematic changes of human knees with osteoarthritis. However, no studies have yet used in-vivo imaging data to approximate material properties of cartilage, and no research has compared the FE output of cartilage loading patterns with in-vivo measurements of cartilage in ACL injured knees. This study developed a subject-specific FE model in knees by using in-vivo T1ρ and morphological data from high–resolution magnetic resonance imaging (MRI). The results of FE simulation demonstrated less stiffness and larger axial strains in articular cartilage with elevated T1ρ. The kinematic changes in ACL–injured knees may affect the load distribution and cause early cartilage degeneration in such joints. In conclusion, the subject-specific FE model is a powerful tool to detect strain distribution, contact area, and contact pressure within the articular cartilage. Novel imaging techniques such as T1ρ MRI coupled with FE analysis may allow for quantification of knee joint biomechanics as well as early detection of cartilage matrix degeneration.

Michelle Grabau
Advisor: Dr. Sharmila Majumdar, PhD
Thesis Title:  Assessment of Porcine Intervertebral Disc Specimen pH via Chemical Exchange Saturation Transfer (CEST) MRI
Abstract:
Low back pain is an expensive, widespread healthcare concern. The mechanisms of its progression and association with intervertebral disc degeneration are not fully understood, but recent studies suggest that lactate accumulation and a subsequent drop in pH may be initiating events. Chemical exchange saturation transfer (CEST) of glycosaminoglycans (gagCEST) has emerged as way to quantify glycosaminoglycan (GAG) concentrations in the intervertebral disc, but no studies have examined its dependency on pH. This study seeks to assess the pH-dependence of gagCEST and use iopromide, a common contrast agent used in CT imaging, as a pH-sensitive CEST probe to explore these agents' potential to measure pH of the intervertebral discs. We first create chondroitin sulfate and UltravistRTM phantoms over a range of pH values to explore the pH-dependency of the CEST imaging of these probes and apply these findings to porcine intervertebral disc specimens. Our results demonstrate the non-linear dependence of gagCEST on pH and a linear regression of the Iopromide CEST effect with pH (R2 = 0.95). Iopromide was then infused into the disc and the calibration created by the phantom studies was used to determine pH in the disc.

These findings provide what is to our knowledge the first description of the pH dependence of gagCEST imaging and the first use of the iopromide contrast agent in the CEST MR imaging of the intervertebral disc specimen. Because iopromide CEST imaging is independent of the local concentration of macromolecules, it particularly shows great potential in reporting pH in intervertebral disc specimen studies. The ability to report pH in a tissue non-invasively by one of these methods could be valuable in better understanding disease progression.

Aditi Guha
Advisor: Dr. Sharmila Majumdar, PhD
Thesis Title:  Rapid Magnetization Prepared Diffusion Weighted Imaging of Articular Cartilage in vivo
Abstract:
Diffusion Imaging has been primarily focused on brain application with limited applications in the knee. One limitation of diffusion imaging in the knee is the long TE (40-60 ms) in most of the sequences that have been used. While this is not a detriment in brain, it can be a problem in the knee where several tissues have short T2 relaxation times including the cartilage (32 ms) and meniscus (11 ms). Thus imaging of the knee with a short TE diffusion sequence would substantially increase signal to noise, which would in turn be applied to improve diffusion measurements in meniscus and cartilage. Research has shown that diffusion weighted imaging in knee has a strong potential as a biomarker and can act as a new and potent investigation tool for tissue integrity of meniscus and for early diagnosis of cartilage degeneration.

A new sequence for diffusion weighted imaging of knee at 3T has been proposed and evaluated. The proposed stimulated echo with MAPSS acquisition sequence is more signal efficient than the conventional spin echo sequence and can image the whole knee volume in half the acquisition time compared to the most commonly used line scan sequence. The sequence was tested in phantoms, ex-vivo specimens andin-vivoknees with encouraging results. Further optimization and validation of the sequence is proposed for successful acquisition of diffusion values in knee cartilage and meniscus in healthy volunteers and osteoarthritis patient cohorts.

Tzu-Cheng Lee
Advisor: Dr. Youngho Seo, PhD
Thesis Title:  Tibia and Vertebra Bone Structure Changes in Old-Male Spontaneously Hypertensive Rats by Quantitative Micro-CT
Abstract:
Studies have shown that hypertension is associated with abnormalities of calcium metabolism, and it may lead to increase the risk of fractures and osteoporosis. However, several recent clinical findings in the past decade revealed an inverse correlation between bone mineral density (BMD) and hypertension in large cohorts of old male subjects. In this report, we further investigated whether this positive correlation between bone loss and hypertension could be also observed in animal models of hypertension. The use of animal models (Spontaneously Hypertensive Rats, SHR) can lead us to a better understanding of the correlation without other confounding factors. We used high-resolution micro-computed tomography to investigate the BMD and bone structure differences in the tibial and vertebral regions of two-year-old male SHRs in comparison to those in normotensive rats (Wistar-Kyoto, WKY). Moreover, we also applied the finite element analysis (FEA) and the bone biomarker test to further examine whether there are significant differences between these two groups. Surprisingly, almost all bone quality indices of the tibial region showed significant statistical differences (p<0.01) between the SHR and the WKY. In the tibial metaphysis part, the SHR group showed significant increase in the bone fraction (BV/TV, 29.5%), bone number (Tb.N, 31.4%), connectivity density of bones (Conn.D, 138%), and decrease in the bone separation (Tb.Sp, -27.9%), cortical thickness (Ct.Th, -18.2%), cortical bone density (Ct.TMD, -1.9%), and structure model index (SMI, -21.6). In addition, the 2-dimensional histomorphometric scan on the tibial diaphysis region also showed that the bone quality is better in SHR than WKY rats. On the contrary, SHRs significantly lost concentrations of two bone formation markers (Vitamin D25H and P1NP), and had elevated S-CTX concentrations (a bone resorption marker) compared to WKYs. In this reports we revealed that even the loss of bone mass continued happening in old-male SHRs, through the changes of bone microarchitectures, the bone quality was getting better at the same time.

Carmin Liang
Advisor: Dr. John Kurhanewicz, PhD
Thesis Title:  Predicting Disease Progression with Multiparametric Magnetic Resonance Imaging of Prostate Cancer Managed with Active Surveillance
Abstract:
Prostate cancer is currently the most prevalent noncutaneous cancer in males. An increase in the number of men diagnosed with indolent, organ-confined disease has lead to the increasing numbers of patients and their physicians selecting active surveillance or "delayed definitive treatment" as a viable approach for managing prostate cancer. However, the selection of appropriate patients for active surveillance has been confounded by sampling errors associated with transrectal ultrasound guided biopsies as well as accurate clinical and imaging biomarkers that predict for aggressive, progressive disease at diagnosis. Multiparametric magnetic resonance (MR) imaging may assist in overcoming this problem; it allows for the identification of the whole gland and a combination of T2-weighted MR imaging, proton MR spectroscopic imaging (1H MRSI), and diffusion-weighted imaging (DWI) can be used to better characterize the aggressiveness of intraglandular cancer at diagnosis. In this retrospective study, we quantitatively analyzed multiparametric MR images from a cohort of active surveillance patients (N=119) to determine the combination of MR imaging techniques that best predicted disease progression on active surveillance. Fifty-nine of 119 patients progressed within 43 +/- 32 months on active surveillance. Receiver-operator characteristic (ROC) curve analysis indicated that all three techniques (T2 MRI, MRSI, DWI) demonstrated similar modest accuracies in predicting progression on AS (AUC of 0.59, 0.63 and 0.61, respectively). The best prediction of prostate cancer progression in AS patients was when all three techniques were positive for cancer presence, yielding an odds ratio for progression of 2.91 (95% CI 1.19 -- 7.08) as compared to all other findings. Whereas a negative finding for all 3 tests for patients that were appropriate for AS yielded an odds ratio for no progression of 2.84 (95% CI = 1.26 -- 6.37) as compared to all other findings. In conclusion, multiparametric MR imaging could play a valuable role in better selecting patients for active surveillance.

Cheng-Liang Liu
Advisor: Dr. Nola Hylton, PhD
Thesis Title:  Comparison Between High-Resolution and Standard DTI in Apparent Diffusion Coefficient and Fractional Anisotropy in Patients with Locally Advanced Breast Cancer
Abstract:
To evaluate fractional anisotropy (FA) in comparison to apparent diffusion coefficient (ADC) for discriminating between cancer and normal breast tissue using standard and high resolution diffusion tensor imaging (DTI). Dynamic contrast enhanced MRI, standard DTI, and high-resolution DTI data were collected in ten patients with locally advanced breast cancer before the start of neoadjuvant treatment. Regions of interest were selected in tumor and ipsilateral normal tissue. ADC and FA values from both DTI sequences were calculated for tumor and normal tissue regions. Additional studies using an ice water phantom were performed to investigate the effects of off iso-center imaging location on quantitative diffusion measurements. ADC values computed from both standard and high-resolution DTI showed a significant difference between normal and tumor tissue (p < 0.0001). A statistically significant difference in FA value for normal and tumor tissue using high resolution DTI was also measured (p = 0.02). Standard DTI measurements of FA did not show a statistically significant difference. Estimates of ADC difference between normal and tumor tissue derived from high-resolution DTI were more accurate than those derived from standard DTI as reflected in narrower 95% confidence intervals. Phantom studies showed deviations of up to 16% (standard DTI) and 19% (high-resolution DTI) in ADC values and 44% (standard DTI) and 258% (high-resolution DTI) in FA values measured in left or right breast coil as off-center locations, as compared to measurements made using a head coil at the magnet iso-center. Both standard and high-resolution DTI sequences found that tumor ADC is significantly lower than ADC of normal tissue. High-resolution DTI also showed that the FA value of tumor is significantly lower than normal tissue. High-resolution DTI sequence might be more sensitive and appears to give superior differentiation between normal tissue and cancer compared to standard DTI.

Manutej Mulaveesala
Advisor: Dr. Tracy McKnight, PhD
Thesis Title:  Quantitative Evaluation of Glioblastoma Multiforme Growth and Treatment with MRI in Murine Models: Tumor Volume, Diffusion Mapping, and T2 Relaxometry
Abstract:
Glioblastoma Multiforme (GBM) is the most common form of primary brain cancer that has an extremely high mortality rate. Imaging has the capacity to serve as a crucial tool for tracking malignant growth and treatment response. Newer, advanced imaging methods such as relaxometry and diffusion have allowed for an extension of traditional anatomical imaging. In this multi-parametric study, murine models were injected with human U87 tumor cells and then scanned using MRI. Three out of six mice were treated while three remained untreated. Using relevant equations for relaxometry and diffusion, a semi-automated post processing tool was created in Matlab that could segment malignant regions of interest (ROI). Diffusion maps and T2 relaxometry maps were created. ROIs from segmentation were used to plot the distribution of T2 and ADC values as a histogram within an area of interest. Tumor volume comparison indicated that the tumor volume was significantly decreased for the treated mice, but the volume did not disappear in any of the treated mice. The distribution data showed that there was a stark change in T2 values following treatment, which was not reflected in the tumor volume, indicating that a shift in T2 values is an earlier marker of treatment response. Following initial treatment, the T2 value distribution was seen to return toward baseline levels, while the tumor volume remained small. Diffusion distributions also indicated that treatment with TMZ had a response. Mean diffusion (MD) and radial diffusion (RD) decreased with treatment, while fractional anisotropy (FA) and longitudinal diffusion (LD) increased in untreated mice. Comparison amongst these diffusion maps indicates that MD and RD show complementary information, as do FA and LD. T-test was applied to compare treated and untreated mice at each week, but there was no statistically significant difference, possibly because the sample size for this study was too small. The pattern evident in the histograms may be significant if more data is acquired to increase the sample size. This study provides new insight to the relevance of using diffusion and T2 values as potential biomarkers for treatment response.