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Light microscopy images of nerves, H&E staining. A Untreated peripheral nerve at 5x magnification. B Treated peripheral nerve (6 mm distal to center of ablation) at 5x magnification showing epineurial collagen homogenization (a), vascular congestion (b), widening of the subperineural space (arrow). C Untreated peripheral nerve 40X detail of axons and Schwann cells. D Treated peripheral nerve 40x detail showing regressive nuclear changes karyolysis (dashed arrow) and pyknosis (arrow) and vacuolization (arrowhead).
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Purpose:
Ultrasound (US)-guided high intensity focused ultrasound (HIFU) has been proposed for noninvasive treatment of neuropathic pain and has been investigated in in-vivo studies. However, ultrasound has important limitations regarding treatment guidance and temperature monitoring. Magnetic resonance (MR)-imaging guidance may overcome these lim...
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Citations
... In a cadaveric and laboratory feasibility study, MRI-guided FUS (MRgHIFU) illustrated temperature elevations of the trigeminal nerve using a gradient echo-sequence (Monteith et al., 2013). Another pilot pig study showed that MRgHIFU with 3D MR neurography guidance could be used for targeted peripheral nerve ablation, such a system could be applicable for posttreatment thermal tracking without contrast injection (Huisman et al., 2015a). Diffusion-weighted imaging and tractography can also effectively visualize target peripheral nerve segments and assess the microstructural changes after MRgHIFU (Walker et al., 2021). ...
Peripheral focused ultrasound stimulation (pFUS) has gained increasing attention in the past few decades, because it can be delivered to peripheral nerves, neural endings, or sub-organs. With different stimulation parameters, ultrasound stimulation could induce different modulation effects. Depending on the transmission medium, pFUS can be classified as body-coupled US stimulation, commonly used for therapeutics or neuromodulation, or as an air-coupled contactless US haptic system, which provides sensory inputs and allows distinct human-computer interaction paradigms. Despite growing interest in pFUS, the underlying working mechanisms remain only partially understood, and many applications are still in their infancy. This review focused on existing applications, working mechanisms, the latest progress, and future directions of pFUS. In terms of therapeutics, large-sample randomized clinical trials in humans are needed to translate these state of art techniques into treatments for specific diseases. The airborne US for human-computer interaction is still in its preliminary stage, but further efforts in task-oriented US applications might provide a promising interaction tool soon.
... Conventional MR sequences, such as T1and T2-weighted imaging, are limited as they cannot selectively visualize peripheral nerves or quantify nerve integrity or injury. Peripheral nerves have been visualized using MR neurography (19) and selective excitation techniques (20), however these approaches do not provide quantitative assessment of nerve changes after treatment. Targeting by atlas or structural images only is also limited in the ability to account for subject variability and specificity in identifying tracts of interest (21). ...
... The results of this study are consistent with previous experiments who reported similar observations of disrupted myelin and axon swelling in the sciatic nerves of pigs (19,46) and rats (7) after treatment with FUS. These authors' observations are based on histology but are reinforced by our analysis of both histology and DTI metrics. ...
... We note that both Huisman et al. and Kaye et al. used large adult pigs (50-75 and 19-40 kg, respectively) with relatively large sciatic nerves (8-10 mm wide) (19,46). Here we demonstrate the ability to image small animals (5-8 kg) and target small nerves (3-4 mm wide) with similar hardware. ...
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 (<1–2 h) treatment effects. Temperature was measured in vivo via MR thermometry. Histological data was collected for lesion assessment.
Results: The sciatic nerves were successfully reconstructed in all subjects. Tract disruption was observed after treatment using both CSD and tensor models. DTI metrics in the targeted nerve segments showed significantly decreased FA and increased MD, AD, and RD. Transducer output power was positively correlated with lesion volume and temperature and negatively correlated with MD, AD, and RD. No correlations were observed between FA and other measured parameters.
Conclusions: DWI and tractography are effective tools for visualizing peripheral nerve segments for targeting in non-invasive surgical methods and for assessing the microstructural changes that occur following MRgFUS treatment.
... Some difficulties exist in visualizing superficial peripheral nerves with MR. In a pilot study, 3D MR neurography showed high potential for guiding HIFU therapy ablation of peripheral nerves [127]. An ultrasound-guided approach for HIFU peripheral nerve block has been demonstrated feasible in an in vivo large-animal study. ...
Chronic pain is one of the leading causes of disability and disease burden worldwide, accounting for a prevalence between 6.9% and 10% in the general population. Pharmacotherapy alone results ineffective in about 70-60% of patients in terms of a satisfactory degree of pain relief. Focused ultrasound is a promising tool for chronic pain management, being approved for thalamotomy in chronic neuropathic pain and for bone metastases-related pain treatment. FUS is a noninvasive technique for neuromodulation and for tissue ablation that can be applied to several tissues. Transcranial FUS (tFUS) can lead to opposite biological effects, depending on stimulation parameters: from reversible neural activity facilitation or suppression (low-intensity, low-frequency ultrasound, LILFUS) to irreversible tissue ablation (high-intensity focused ultrasounds, HIFU). HIFU is approved for thalamotomy in neuropathic pain at the central nervous system level and for the treatment of facet joint osteoarthritis at the peripheral level. Potential applications include HIFU at the spinal cord level for selected cases of refractory chronic neuropathic pain, knee osteoarthritis, sacroiliac joint disease, intervertebral disc nucleolysis, phantom limb, and ablation of peripheral nerves. FUS at nonablative dosage, LILFUS, has potential reversible and tissue-selective effects. FUS applications at nonablative doses currently are at a research stage. The main potential applications include targeted drug and gene delivery through the Blood-Brain Barrier, assessment of pain thresholds and study of pain, and reversible peripheral nerve conduction block. The aim of the present review is to describe the approved and potential applications of the focused ultrasound technology in the field of chronic pain management.
... The authors evaluated the theranostic platform using a triple-vial phantom. In addition to localizing the MNPs, MRI has successfully been used to monitor the temperature during different thermal therapies [9], [10]- [12]. Although MR thermometry is real-time and provides temperature maps in a wide range of temperatures, it is a very complex and high-cost technique [13]. ...
Objective:
Nanotheranostic systems integrate therapeutic and diagnostic procedures using nanotechnology. This type of approach has enabled the development of methods for early detection and treatment of different pathologies. Magnetic hyperthermia (MH) has been proposed as an alternative or complementary method of cancer therapy. However, challenges such as delivering and localizing the magnetic nanoparticles (MNPs) within tissues and monitoring the temperature during the treatment hinder this technique to be effectively translated into clinical routine. Therefore, in this study a theranostic platform has been proposed and examined to address two main issues, localizing MNPs and real-time temperature monitoring, for preclinical MH.
Methods:
The system integrates magnetomotive (MMUS) and thermal ultrasound imaging with MH. An ultrasound device was used to acquire MMUS images to detect MNPs, and ultrasound thermometry to monitor the temperature. This platform was designed such that a single coil generated the magnetic field for MMUS and MH. The feasibility of the system was examined using a tissue mimicking phantom containing an inclusion filled with zinc substituted magnetite NPs.
Results:
These MNPs were effectively used as contrast agent for MMUS and to generate heat during MH. In addition to localizing MNPs, real-time two-dimensional temperature maps were obtained with substantial concordance (pc>0.97) with invasive measurements using fiber optic thermometer. The heating rate was proportional to the displacements in MMUS (r=0.92).
Conclusion:
Ultrasound thermometry was successfully used to monitor the temperature during MH. In addition, it was shown that acquiring MMUS images prior to MH can qualitatively predict the temperature distribution of the MNP-laden regions.
... The histologic results of HIFU when treating nerve injuries show that heat radiation can cause high edema of nerve bundles, prominent degeneration and necrosis of the cell axis, and increased eosinophils in the cytoplasm. Thermal lesions were radiographically visible as focal hyperintense regions before contrast injection on post-treatment MR neurography and as non-enhancing regions with rim-enhancement at the periphery by MRI evaluation [34]. In terms of the change of the gray scale produced by target tissue, an indicator of tissue deterioration and necrosis, the criteria for evaluating the efficacy of the ultrasonic treatment in the before and after treatment of gray-scale changes in the treatment area can be established [17]. ...
Primary trigeminal neuralgia is a common clinical refractory neuralgia characterized by an onset of excruciating pain that can severely affect patients’ quality of life. Long-term suffering from this pain may lead to depression, anxiety, and suicide. Current treatments, however, are associated with high recurrent rates and severe complications.
We hypothesize that both the applicability and efficacy of magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) treatment in primary trigeminal neuralgia can be achieved under the following conditions: a specific target focus and incident channel, a temperature measurement system that does not incur damage to surrounding tissues, and an optimal radiation dose. Successful non-invasive treatment of primary trigeminal neuralgia by MR-HIFU systems could represent a breakthrough of this technology applied to the oral and maxillofacial region.
... 7,12,14 Magnetic resonance imagingeguided focused ultrasound for the treatment of facet joint osteoarthritis has been reported in a few small human series and swine models, with promising early results. 7,[15][16][17] The procedure is currently being performed as part of routine clinical care at selected centers in Europe and Asia. 18 Published reports evaluating the ability of MRgFUS to improve treatment response in patients with proven facet joint pain but limited durability of response to other treatments are lacking. ...
Magnetic resonance imaging–guided focused ultrasound (MRgFUS) is a noninvasive modality that allows for precise tissue ablation with sparing of surrounding structures. Early reports of the use of MRgFUS for the treatment of facet joint osteoarthritis are promising. We present a case of facet joint pain treated successfully by MRgFUS at our institution. Magnetic resonance imaging–guided focused ultrasonography may be a useful modality for patients with facet joint–mediated low back pain, particularly in the setting of limited or refractory response to conventional treatments.
... The position of nervous tissue on imaging slices can be revealed in relation to surrounding anatomy without the need for registration to anatomical images as is typically done between DWI and T1 or T2. This provides anatomical references for nerve positioning in non-invasive surgical procedures [146,194]. MR neurography does not, however, convey specific connectivity information between regions as is available in three-dimensional DWI virtual dissection techniques. It also does not permit quantitative assessment of tissue microstructure via DTI metrics. ...
... Conventional MR sequences, such as T1-and T2-weighted imaging, are limited as they cannot selectively visualize peripheral nerves or quantify nerve integrity or injury [235,439]. Peripheral nerves have been visualized using MR neurography [194,441,443] and selective excitation techniques [55,471], however these approaches also do not provide quantitative assessment of nerve changes after treatment. ...
... Giles with similar hardware. These smaller nerves reflect a similar size to potential human clinical MRgFUS targets such as the pudendal nerve [365] or posterior femoral cutaneous nerve [145], as noted by Huisman et al. [194]. ...
Magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive treatment modality which uses acoustic waves to generate precise thermal lesions. There is growing interest in its application to the treatment of neurological conditions. Conventional MR contrasts can provide anatomical references for targeting and lesion identification but do not impart information about the cellular environment or neural microstructure. Diffusion weighted imaging (DWI) is a technique sensitive to the motion of water within tissue that can be used to visualize fiber bundles and quantitatively assess treatment changes to nerve architecture in vivo. The main aims of this thesis are to: 1) develop an imaging and acoustic sonication procedure using DWI and tractography; and 2) incorporate DWI in the thermal lesioning of intracranial white matter and peripheral nerves to enhance targeting and understand the treatment effect on tissue microstructure. Specific aims of this thesis are to: 1) investigate the DWI characteristics of ex vivo animal brain tissue as a model for neurosurgical treatment development; 2) generate thermal lesions on brain white matter in an in vivo animal model and determine the treatment effect via diffusion tensor imaging (DTI) metrics, tractography, and histological validation; 3) reconstruct the sciatic nerves via tractography to enhance target determination; and 4) produce focal ablations on the sciatic nerve and measure the microstructural changes via DTI metrics. Imaging results from Study I reveal that non-fixed ex vivo brain tissue does not differ from in vivo tissue in terms of diffusion anisotropy, demonstrating its potential use in neurosurgical technique characterization. In Study II, lesion size and location were automatically determined in vivo using Mean DWI and confirmed by histology. DTI metrics in the lesion revealed a pattern of treatment-related anisotropy and diffusivity alterations. Affected fiber pathways were visualized via tractography. In Study III, higher order tractography methods permitted consistent reconstruction of sciatic nerves and precise MRgFUS target placement. Significant microstructural changes in the nerve were observed due to lesioning. Taken together, this thesis demonstrates significant advancements in the visualization of MRgFUS treatment targets and the assessment of microstructural changes that occur following thermal ablation within the central and peripheral nervous systems.
https://hdl.handle.net/1807/97714
... First, the original RGB (red-green-blue) images were used to extract the white spaces. Second, each image was transformed from the RGB to the YUV (luminance-bandwidth-chrominance) color space to more easily separate the blue from the purple areas, indicating collagen (CL) and myelin (ML), respectively (Huisman, et al. 2015, Turedi, et al. 2018). In the case of the V chrominance component of the YUV color space, blue corresponds to the opposite part of the color spectrum than purple. ...
We investigate the usefulness of quantitative ultrasound (QUS) and B-mode texture features for characterization of ulnar nerve fascicles. Ultrasound data were acquired from cadaveric specimens using a nominal 30 MHz probe. Next, the nerves were extracted to prepare histology sections. 85 fascicles were matched between the B-mode images and the histology sections. For each fascicle image, we selected an intra-fascicular region of interest. We used histology sections to determine features related to the concentration of collagen and myelin, and ultrasound data to calculate backscatter coefficient (-24.89 dB $\pm$ 8.31), attenuation coefficient (0.92 db/cm-MHz $\pm$ 0.04), Nakagami parameter (1.01 $\pm$ 0.18) and entropy (6.92 $\pm$ 0.83), as well as B-mode texture features obtained via the gray level co-occurrence matrix algorithm. Significant Spearman's rank correlations between the combined collagen and myelin concentrations were obtained for the backscatter coefficient (R=-0.68), entropy (R=-0.51), and for several texture features. Our study demonstrates that QUS may potentially provide information on structural components of nerve fascicles.
... First, the original RGB (red-green-blue) images were used to extract the white spaces. Second, each image was transformed from the RGB to the YUV (luminance-bandwidth-chrominance) color space to more easily separate the blue from the purple areas, indicating collagen (CL) and myelin (ML), respectively (Huisman, et al. 2015, Turedi, et al. 2018). In the case of the V chrominance component of the YUV color space, blue corresponds to the opposite part of the color spectrum than purple. ...
We investigate the usefulness of quantitative ultrasound (QUS) and B-mode texture features for characterization of ulnar nerve fascicles. Ultrasound data were acquired from cadaveric specimens using a nominal 30 MHz probe. Next, the nerves were extracted to prepare histology sections. 85 fascicles were matched between the B-mode images and the histology sections. For each fascicle image, we selected an intra-fascicular region of interest. We used histology sections to determine features related to the concentration of collagen and myelin, and ultrasound data to calculate backscatter coefficient (-24.89 dB ± 8.31), attenuation coefficient (0.92 db/cm-MHz ± 0.04), Nakagami parameter (1.01 ± 0.18) and entropy (6.92 ± 0.83), as well as B-mode texture features obtained via the gray level co-occurrence matrix algorithm. Significant Spearman’s rank correlations between the combined collagen and myelin concentrations were obtained for the backscatter coefficient (R=-0.68), entropy (R=-0.51), and for several texture features. Our study demonstrates that QUS may potentially provide information on structural components of nerve fascicles.
... This is to its detriment, as complex tissue structures can cause the focal region to shift, widen, split, or fail to appear at all [64]. To mitigate the risks arising from inaccurate plans, treatments must be carefully monitored using magnetic resonance (MR) thermometry [57] or ultrasound imaging [106], and manually corrected when the acoustic waves fail to focus as intended. These monitoring techniques are not ideal. ...
High-intensity focussed ultrasound (HIFU) is an emerging cancer therapy that holds great promise, as it is minimially invasive, requires no ionising radiation, and can treat small volumes precisely. However, currently therapies are hindered by an inadequate capacity for treatment planning, as the interactions between the sound waves and tissue are complex and difficult to simulate. The Fourier pseudospectral method is one way of efficiently performing these simulations, as it can provide high accuracies with low computational costs. However, it is typically used with uniform computational meshes, wasting resolution in regions of the simulation where only low frequencies are present, and typically under-resolving the acoustic field in the focal region. This thesis addresses this problem in two ways: First, a bandwidth-based measure of the spatial resolution requirements for a model solution is developed and integrated into a moving mesh method. This allows spatially and temporally-varying resolution requirements to be met. Bandwidth-based meshes are shown to perform very well when compared with current mesh adaptation approaches. Second, a technique is presented for discretising arbitrary acoustic source distributions that does not rely on the source's region of support coinciding with the mesh. This not only allows sources to be represented with adaptive meshes, but greatly improves the accuracy of source discretisations for uniform meshes as well. These two contributions are of vital importance in the context of HIFU simulation, and can easily be applied to the many other problems for which the Fourier pseudospectral method is used.
