Testing the Efficacy of Contrast-Enhanced Ultrasound in Detecting Transplant Rejection Using a Murine Model of Heart Transplantation.

One of the key unmet needs to improve long-term outcomes of heart transplantation is to develop accurate, noninvasive, and practical diagnostic tools to detect transplant rejection. Early intragraft inflammation and endothelial cell injuries occur prior to advanced transplant rejection. We developed a novel diagnostic imaging platform to detect early declines in microvascular perfusion (MP) of cardiac transplants using contrast-enhanced ultrasonography (CEUS). The efficacy of CEUS in detecting transplant rejection was tested in a murine model of heart transplants, a standard preclinical model of solid organ transplant. As compared to the syngeneic groups, a progressive decline in MP was demonstrated in the allografts undergoing acute transplant rejection (40%, 64%, and 92% on days 4, 6, and 8 posttransplantation, respectively) and chronic rejection (33%, 33%, and 92% on days 5, 14, and 30 posttransplantation, respectively). Our perfusion studies showed restoration of MP following antirejection therapy, highlighting its potential to help monitor efficacy of antirejection therapy. Our data suggest that early endothelial cell injury and platelet aggregation contributed to the early MP decline observed in the allografts. High-resolution MP mapping may allow for noninvasive detection of heart transplant rejection. The data presented have the potential to help in the development of next-generation imaging approaches to diagnose transplant rejection.

MR imaging-guided focused ultrasound surgery of fibroadenomas in the breast: a feasibility study.

PURPOSE: To test the feasibility of noninvasive magnetic resonance (MR) imaging-guided focused ultrasound surgery (FUS) of benign fibroadenomas in the breast. MATERIALS AND METHODS: Eleven fibroadenomas in nine patients under local anesthesia were treated with MR imaging-guided FUS. Based on a T2-weighted definition of target volumes, sequential sonications were delivered to treat the entire target. Temperature-sensitive phase-difference-based MR imaging was performed during each sonication to monitor focus localization and tissue temperature changes. After the procedure, T2-weighted and contrast material-enhanced T1-weighted MR imaging were performed to evaluate immediate and long-term effects. RESULTS: Thermal imaging sequences were improved over the treatment period, with 82% (279 of 342) of the hot spots visible in the last seven treatments. The MR imager was used to measure temperature elevation (12.8 degrees -49.9 degrees C) from these treatments. Eight of the 11 lesions treated demonstrated complete or partial lack of contrast material uptake on posttherapy T1-weighted images. Three lesions showed no marked decrease of contrast material uptake. This lack of effective treatment was most likely due to a lower acoustic power and/or patient movement that caused misregistration. No adverse effects were detected, except for one case of transient edema in the pectoralis muscle 2 days after therapy. CONCLUSION: MR imaging-guided FUS can be performed to noninvasively coagulate benign breast fibroadenomas.

Usefulness of MR imaging-derived thermometry and dosimetry in determining the threshold for tissue damage induced by thermal surgery in rabbits.

PURPOSE: To investigate in vivo the feasibility of using magnetic resonance (MR) imaging-derived temperature and thermal dose measurements to find the threshold of thermal tissue damage. MATERIALS AND METHODS: Sonications were delivered in rabbit thigh muscles at varying powers. Temperature-sensitive MR images obtained during the sonications were used to estimate the temperature and thermal dose. The temperature, thermal dose, and applied power were then correlated to the occurrence of tissue damage observed on postsonication images. An eight-element phased-array transducer was used to produce spatially flat temperature profiles that allowed for averaging to reduce the effects of noise and the voxel size. RESULTS: The occurrence of tissue damage correlated well with the MR imaging-derived temperature and thermal dose measurements but not with the applied power. Tissue damage occurred at all locations with temperatures greater than 50.4 degrees C and thermal doses greater than 31.2 equivalent minutes at 43.0 degrees C. No tissue damage occurred when these values were less than 47.2 degrees C and 4.3 equivalent minutes. CONCLUSION: MR imaging thermometry and dosimetry provide an index to predict the threshold for tissue damage in vivo. This index offers improved online control over minimally invasive thermal treatments and should allow for more accurate target volume coagulation.

Magnetic resonance image-guided thermal ablations.

Magnetic resonance imaging (MRI)-based monitoring has been shown in recent years to enhance the effectiveness of minimally or noninvasive thermal therapy techniques, such as laser, radiofrequency, microwave, ultrasound, and cryosurgery. MRI's unique soft-tissue contrast and ability to image in three dimensions and in any orientation make it extremely useful for treatment planning and probe localization. The temperature sensitivity of several intrinsic parameters enables MRI to visualize and quantify the progress of ongoing thermal treatment. MRI is sensitive to thermally induced tissue changes resulting from the therapies, giving the physician a method to determine the success or failure of the treatment. These methods of using MRI for planning, guiding, and monitoring thermal therapies are reviewed.

Determination of the optimal delay between sonications during focused ultrasound surgery in rabbits by using MR imaging to monitor thermal buildup in vivo.

PURPOSE: To use magnetic resonance (MR) imaging to monitor thermal buildup and its effects in treated tissues during sequentially delivered sonications in vivo to optimize the intersonication delay for any set of ultrasound and tissue parameters. MATERIALS AND METHODS: Sequential sonications were delivered next to each other in both thighs in 10 male New Zealand white rabbits. The time between sonications was 11-60 seconds. Phase-difference MR imaging was used to monitor temperature rise, which was used to estimate the thermal dose delivered to the tissue. T2-weighted and contrast agent-enhanced T1-weighted imaging were used to gauge the extent of tissue coagulation. RESULTS: With a short intersonication delay (11-40 seconds), the estimated temperature rise and the extent of tissue coagulation increased dramatically in subsequent sonications. However, when the delay was long (50-60 seconds), the size and shape of the destroyed tissue with subsequent sonications was uniform, and the temperature buildup was substantially lower. CONCLUSION: MR imaging can be used to monitor thermal buildup and its effects due to sequential, neighboring sonications in vivo to produce evenly shaped regions of tissue coagulation. The temperature information obtained from the monitoring can be used to optimize the intersonication delay for any set of ultrasound and tissue parameters.

Tissue temperature monitoring with multiple gradient-echo imaging sequences.

The inherent sensitivity of multiple gradient-echo sequences to the chemical shift is exploited to rapidly map muscle water frequency shifts caused by ultrasonic heating. The use of multiple echoes is shown to offer several advantages over single gradient-echo approaches previously proposed for temperature measurement. An increase in the effective bandwidth significantly reduces aliasing problems observed with single gradient-echo methods in high temperature applications. Of greater significance is the improved immunity to intrascan motion found for multi-echo versus single echo gradient methods, making the former more attractive for clinical applications. Finally, a sensitivity to the presence of multiple spectral components unavailable with single gradient-echo methods is obtained.