Search

AbstractIntroduction Magnetic Resonance-guided Focused Ultrasound (MRgFUS) thermal ablation is an effective noninvasive ultrasonic therapy to disrupt in vivo porcine tendon but is prone to inducing skin burns. We evaluated the safety profile of a novel hybrid protocol that minimizes thermal spread by combining long-pulse focused ultrasound followed by thermal ablation.Methods In-vivo Achilles tendons (hybrid N = 15, thermal ablation alone N = 21) from 15 to 20 kg Yorkshire pigs were randomly assigned to 6 treatment groups in two studies. The first (N = 21) was ablation (600, 900, or 1200 J). The second (N = 15) was hybrid: pulsed FUS (13.5 MPa peak negative pressure) followed by ablation (600, 900, or 1200 J). Measurements of ankle range of motion, tendon temperature, thermal dose (240 CEM43), and assessment of skin burn were performed in both groups.Results Rupture was comparable between the two protocols: 1/5 (20%), 5/5 (100%) and 5/5 (100%) for hybrid protocol, compared to 2/7 (29%), 6/7 (86%) and 7/7 (100%) for the ablation-only protocol with energies of 600, 900, and 1200 J, respectively. The hybrid protocol produced lower maximum temperatures, smaller areas of thermal dose, fewer thermal injuries to the skin, and fewer full-thickness skin burns. The standard deviation for the area of thermal injury was also smaller for the hybrid protocol, suggesting greater predictability.Conclusion This study demonstrated a hybrid MRgFUS protocol combining long-pulse FUS followed by thermal ablation to be noninferior and safer than an ablation-only protocol for extracorporeal in-vivo tendon rupture for future clinical application for noninvasive release of contracted tendon.

AbstractPurpose Surgical resection of the tendon is an effective treatment for severe contracture. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is a non-invasive ultrasonic therapy which produces a focal increase in temperature, subsequent tissue ablation and disruption. We evaluated MRgFUS as a clinically translatable treatment modality to non-invasively disrupt in vivo porcine tendons.Material and methods In vivo Achilles tendons (n = 28) from 15–20kg Yorkshire pigs (n = 16) were randomly assigned to 4 treatment groups of 600, 900, 1200 and 1500 J. Pretreatment range of motion (ROM) of the ankle joint was measured with the animal under general anesthesia. Following MRgFUS treatment, success of tendon rupture, ROM increase, temperature, thermal dosage, skin burn, and histology analyses were performed.Results Rupture success was found to be 29%, 86%, 100% and 100% for treatment energies of 600, 900, 1200 and 1500 J respectfully. ROM difference at 90° flexion showed a statistically significant change in ROM between 900 J and 1200 J from 16° to 27°. There was no statistical significance between other groups, but there was an increase in ROM as more energy was delivered in the treatment. For each of the respective treatment groups, the maximal temperatures were 58.4 °C, 63.3 °C, 67.6 °C, and 69.9 °C. The average areas of thermal dose measured were 24.3mm2, 53.2mm2, 77.8mm2 and 91.6mm2. The average areas of skin necrosis were 5.4mm2, 21.8mm2, 37.2mm2, and 91.4mm2. Histologic analysis confirmed tissue ablation and structural collagen fiber disruption.Conclusions This study demonstrated that MRgFUS is able to disrupt porcine tendons in vivo without skin incisions.

Objectives: Magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive targeted tissue ablation technique that can be applied to the nervous system. Diffusion weighted imaging (DWI) can visualize and evaluate nervous system microstructure. Tractography algorithms can reconstruct fiber bundles which can be used for treatment navigation and diffusion tensor imaging (DTI) metrics permit the quantitative assessment of nerve microstructure in vivo. There is a need for imaging tools to aid in the visualization and quantitative assessment of treatment-related nerve changes in MRgFUS. We present a method of peripheral nerve tract reconstruction and use DTI metrics to evaluate the MRgFUS treatment effect.Materials and Methods: MRgFUS was applied bilaterally to the sciatic nerves in 6 piglets (12 nerves total). T1-weighted and diffusion images were acquired before and after treatment. Tensor-based and constrained spherical deconvolution (CSD) tractography algorithms were used to reconstruct the nerves. DTI metrics of fractional anisotropy (FA), and mean (MD), axial (AD), and radial diffusivities (RD) were measured to assess acute (

Objectives: The application of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of neurological conditions has been of increasing interest. Conventional MR imaging can provide structural information about the effect of MRgFUS, where differences in ablated tissue can be seen, but it lacks information about the status of the cellular environment or neural microstructure. We investigate in vivo acute changes in water diffusion and white matter tracts in the brain of a piglet model after MRgFUS treatment using diffusion-weighted imaging (DWI) with histological verification of treatment-related changes.Methods: MRgFUS was used to treat the anterior body of the fornix in four piglets. T1 and diffusion-weighted images were collected before and after treatment. Mean diffusion-weighted imaging (MDWI) images were generated to measure lesion volumes via signal intensity thresholds. Histological data were collected for volume comparison and assessment of treatment effect. DWI metric maps of fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) were generated for quantitative assessment. Fornix-related fiber tracts were generated before and after treatment for qualitative assessment.Results: The volume of treated tissue measured via MDWI did not differ significantly from histological measurements, and both were significantly larger than the treatment cell volume. Diffusion metrics in the treatment region were significantly decreased following MRgFUS treatment, with the peak change seen at the lesion core and decreasing radially. Histological analysis confirmed an area of coagulative necrosis in the targeted region with sharp demarcation zone with surrounding brain. Tractography from the lesion core and the fornix revealed fiber disruptions following treatment.Conclusions: Diffusion maps and fiber tractography are an effective method for assessing lesion volumes and microstructural changes in vivo following MRgFUS treatment. This study demonstrates that DWI has the potential to advance MRgFUS by providing convenient in vivo microstructural lesion and fiber tractography assessment after treatment.

PURPOSE:Diffusion magnetic resonance imaging and tractography has an important role in the visualization of brain white matter and assessment of tissue microstructure. There is a lack of correspondence between diffusion metrics of live tissue, ex vivo tissue, and histological findings. The objective of this study is to elucidate this connection by determining the specific diffusion alterations between live and ex vivo brain tissue. This may have an important role in the incorporation of diffusion imaging in ex vivo studies as a complement to histological sectioning as well as investigations of novel neurosurgical techniques. METHODS:This study presents a method of high angular resolution diffusion imaging and tractography of intact and non-fixed ex vivo piglet brains. Most studies involving ex vivo brain specimens have been formalin-fixed or excised from their original biological environment, processes both of which are known to affect diffusion parameters. Thus, non-fixed ex vivo tissue is used. A region-of-interest based analysis of diffusion tensor metrics are compared to in vivo subjects in a selection of major white matter bundles in order to assess the translatability of ex vivo diffusion measurements. RESULTS:Tractography was successfully achieved in both in vivo and ex vivo groups. No significant differences were found in tract connectivity, average streamline length, or apparent fiber density. Significantly decreased diffusivity (mean, axial, and radial; p0.059) between groups were observed. CONCLUSION:This study validates the extrapolation of non-fixed fractional anisotropy measurements to live tissue and the potential use of ex vivo tissue for methodological development.

An increasing number of applications use the postnatal piglet model in neuroimaging studies, however these are based primarily on T1 weighted image templates. There is a growing need for a multimodal structural brain template for a comprehensive depiction of the piglet brain, particularly given the growing applications of diffusion weighted imaging for characterizing tissue microstructures and white matter organization. In this study, we present the first multimodal piglet structural brain template which includes a T1 weighted image with tissue segmentation probability maps, diffusion weighted metric templates with multiple diffusivity maps, and population-based whole-brain fiber tracts for postnatal piglets. These maps provide information about the integrity of white matter that is not available in T1 images alone. The availability of this diffusion weighted metric template will contribute to the structural imaging analysis of the postnatal piglet brain, especially models that are designed for the study of white matter diseases. Furthermore, the population-based whole-brain fiber tracts permit researchers to visualize the white matter connections in the piglet brain across subjects, guiding the delineation of a specific white matter region for structural analysis where current diffusion data is lacking. Researchers are able to augment the tracts by merging tracts from their own data to the population-based fiber tracts and thus improve the confidence of the population-wise fiber distribution.