Non-Cartesian MR Microscopy for Cancer Imaging in Small Animals

<p>Mouse models of cancer are an invaluable tool for studying the mechanism of the disease and the effect of new therapies. Recent years have seen an explosive growth in the development of such models and consequently there is an increased need for better imaging techniques to study them. The goal of this work was to develop a technique that satisfied the requirements for preclinical cancer imaging: high spatial resolution, good soft tissue differentiation, excellent motion immunity, fast and non-invasive imaging to enable high-throughput, longitudinal studies. </p> <p>T₂-weighted and diffusion-weighted magnetic resonance imaging (MRI) has been shown to be effective for tumor characterization clinically. But translation of these techniques to the mouse is challenging. The higher spatial resolution and faster physiologic motion make conventional approaches very susceptible to phase artifacts. Additionally, at higher magnetic fields required for these studies, T<super>*</super>₂ and T₂ are significantly shorter and T₁ is longer, making in vivo imaging even harder.</p> <p>A rigorous cancer imaging protocol was developed by optimizing and integrating various components of the system, including MR hardware, animal handling, and pulse sequence design to achieve reliable, repeatable and rapid imaging. The technique presented here relies heavily on the non-Cartesian sampling strategy of PROPELLER (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction) MRI. The novel data acquisition and reconstruction overcomes the adverse effects of physiological motion, allows for rapid setup and acquisition and provides excellent tissue contrast. The sequence was optimized to enable T₂-weighted and diffusion-weighted imaging in tumor-bearing mice with in-plane resolution of 117&mu;m and slice thickness of 1mm. Multi-slice datasets covering the entire thorax and abdomen were acquired in &sim;30 minutes.</p> <p>The imaging protocol developed here was applied to a high-throughput, longitudinal study in a mouse model of liver metastases. The liver is a common site of distal metastases in colon and rectal cancer, and if detected early has an improved prognosis. Unfortunately, severe respiratory motion make it hard to image. The relative merits of the proposed PROPELLER technique were analyzed with respect to the accepted gold-standard for abdominal cancer imaging, computed tomography (CT).</p> <p>The non-Cartesian MR microscopy technique proposed here is a valuable tool in the &ldquo;Cancer analysis toolkit&rdquo;. It allows for high-throughput, longitudinal experiments in free-breathing mice generating both structural and functional information with minimal artifacts and excellent spatial resolution. This work should find broad applications in various mouse models of cancer for studying the pathology of the disease, its progression as well as its response to treatment.</p>Dissertatio

T1ρ and T2 -based characterization of regional variations in intervertebral discs to detect early degenerative changes.

Lower back pain is one of the main contributors to morbidity and chronic disability in the United States. Despite the significance of the problem, it is still not well understood. There is a clear need for objective, non-invasive biomarkers to localize specific pain generators and identify early stage changes to enable reliable diagnosis and treatment. In this study we focus on intervertebral disc degeneration as a source of lower back pain. Quantitative imaging markers T1ρ and T2 have been shown to be promising techniques for in vivo diagnosis of biochemical degeneration in discs due to their sensitivity to macromolecular changes in proteoglycan content and collagen integrity. We describe a semi-automated technique for quantifying T1ρ and T2 relaxation time maps in the nucleus pulposus (NP) and the annulus fibrosus (AF) of the lumbar intervertebral discs. Compositional changes within the NP and AF associated with degeneration occur much earlier than the visually observable structural changes. The proposed technique rigorously quantifies these biochemical changes taking into account subtle regional variations to allow interpretation of early degenerative changes that are difficult to interpret with traditional MRI techniques and clinical subjective grading scores. T1ρ and T2 relaxation times in the NP decrease with degenerative severity in the disc. Moreover, standard deviation and texture measurements of these values show sharper and more significant changes during early degeneration compared to later degenerative stages. Our results suggest that future prospective studies should include automated T1ρ and T2 metrics as early biomarkers for disc degeneration-induced lower back pain. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1373-1381, 2016

Caspase-responsive smart gadolinium-based contrast agent for magnetic resonance imaging of drug-induced apoptosis

Non-invasive detection of caspase-3/7 activity in vivo has provided invaluable predictive information regarding tumor therapeutic efficacy and anti-tumor drug selection. Although a number of caspase-3/7 targeted fluorescence and positron emission tomography (PET) imaging probes have been developed, there is still a lack of gadolinium (Gd)-based magnetic resonance imaging (MRI) probes that enable high spatial resolution detection of caspase-3/7 activity in vivo. Here we employ a self-assembly approach and develop a caspase-3/7 activatable Gd-based MRI probe for monitoring tumor apoptosis in mice. Upon reduction and caspase-3/7 activation, the caspase-sensitive nano-aggregation MR probe (C-SNAM: 1) undergoes biocompatible intramolecular cyclization and subsequent self-assembly into Gd-nanoparticles (GdNPs). This results in enhanced r1 relaxivity-19.0 (post-activation) vs. 10.2 mM-1 s-1 (pre-activation) at 1 T in solution-and prolonged accumulation in chemotherapy-induced apoptotic cells and tumors that express active caspase-3/7. We demonstrate that C-SNAM reports caspase-3/7 activity by generating a significantly brighter T1-weighted MR signal compared to non-treated tumors following intravenous administration of C-SNAM, providing great potential for high-resolution imaging of tumor apoptosis in vivo

Caspase-responsive smart gadolinium-based contrast agent for magnetic resonance imaging of drug-induced apoptosis

Non-invasive detection of caspase-3/7 activity in vivo has provided invaluable predictive information regarding tumor therapeutic efficacy and anti-tumor drug selection. Although a number of caspase-3/7 targeted fluorescence and positron emission tomography (PET) imaging probes have been developed, there is still a lack of gadolinium (Gd)-based magnetic resonance imaging (MRI) probes that enable high spatial resolution detection of caspase-3/7 activity in vivo. Here we employ a self-assembly approach and develop a caspase-3/7 activatable Gd-based MRI probe for monitoring tumor apoptosis in mice. Upon reduction and caspase-3/7 activation, the caspase-sensitive nano-aggregation MR probe (C-SNAM: 1) undergoes biocompatible intramolecular cyclization and subsequent self-assembly into Gd-nanoparticles (GdNPs). This results in enhanced r(1) relaxivity—19.0 (post-activation) vs. 10.2 mM(−1) s(−1) (pre-activation) at 1 T in solution—and prolonged accumulation in chemotherapy-induced apoptotic cells and tumors that express active caspase-3/7. We demonstrate that C-SNAM reports caspase-3/7 activity by generating a significantly brighter T(1)-weighted MR signal compared to non-treated tumors following intravenous administration of C-SNAM, providing great potential for high-resolution imaging of tumor apoptosis in vivo

Higher glucose, insulin and insulin resistance (HOMA-IR) in childhood predict adverse cardiovascular risk in early adulthood: the Pune Children's Study

AIMS/HYPOTHESIS:The Pune Children's Study aimed to test whether glucose and insulin measurements in childhood predict cardiovascular risk factors in young adulthood.METHODS:We followed up 357 participants (75% follow-up) at 21 years of age who had undergone detailed measurements at 8 years of age (glucose, insulin, HOMA-IR and other indices). Oral glucose tolerance, anthropometry, plasma lipids, BP, carotid intima-media thickness (IMT) and arterial pulse wave velocity (PWV) were measured at 21 years.RESULTS:Higher fasting glucose, insulin and HOMA-IR at 8 years predicted higher glucose, insulin, HOMA-IR, BP, lipids and IMT at 21 years. A 1 SD change in 8 year variables was associated with a 0.10-0.27 SD change at 21 years independently of obesity/adiposity at 8 years of age. A greater rise in glucose-insulin variables between 8 and 21 years was associated with higher cardiovascular risk factors, including PWV. Participants whose HOMA-IR measurement remained in the highest quartile (n = 31) had a more adverse cardiovascular risk profile compared with those whose HOMA-IR measurement remained in the lowest quartile (n = 28).CONCLUSIONS/INTERPRETATION:Prepubertal glucose-insulin metabolism is associated with adult cardiovascular risk and markers of atherosclerosis. Our results support interventions to improve glucose-insulin metabolism in childhood to reduce cardiovascular risk in later life

Abstracts of AICTE Sponsored International Conference on Post-COVID Symptoms and Complications in Health

This book presents the selected abstracts of the International Conference on Post-COVID Symptoms and Complications in Health, hosted from the 28th to 29th of April 2022 in virtual mode by the LR Institute of Pharmacy, Solan (H.P.)-173223 in Collaboration with AICTE, New Delhi. This conference focuses on the implications of long-term symptoms on public health, ways to mitigate these complications, improve understanding of the disease process in COVID-19 patients, use of computational methods and artificial intelligence in predicting complications, and the role of various drug delivery systems in combating the complications. Conference Title:  International Conference on Post-COVID Symptoms and Complications in HealthConference Sponsor: AICTE, New Delhi.Conference Date: 28-29 April 2022Conference Location: OnlineConference Organizer: LR Institute of Pharmacy, Solan (H.P.)-173223

Abstracts of AICTE Sponsored International Conference on Post-COVID Symptoms and Complications in Health

This book presents the selected abstracts of the International Conference on Post-COVID Symptoms and Complications in Health, hosted from the 28th to 29th of April 2022 in virtual mode by the LR Institute of Pharmacy, Solan (H.P.)-173223 in Collaboration with AICTE, New Delhi. This conference focuses on the implications of long-term symptoms on public health, ways to mitigate these complications, improve understanding of the disease process in COVID-19 patients, use of computational methods and artificial intelligence in predicting complications, and the role of various drug delivery systems in combating the complications. Conference Title:  International Conference on Post-COVID Symptoms and Complications in HealthConference Sponsor: AICTE, New Delhi.Conference Date: 28-29 April 2022Conference Location: OnlineConference Organizer: LR Institute of Pharmacy, Solan (H.P.)-173223