Noninvasive release of tendons using MRI guided focused ultrasound: a hybrid therapy using long-pulse focused ultrasound followed by thermal ablation.

INTRODUCTION: 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.

Biomechanical testing of ex vivo porcine tendons following high intensity focused ultrasound thermal ablation.

INTRODUCTION: Magnetic resonance-guided focused ultrasound (MRgFUS) has been demonstrated to be able to thermally ablate tendons with the aim to non-invasively disrupt tendon contractures in the clinical setting. However, the biomechanical changes of tendons permitting this disrupting is poorly understood. We aim to obtain a dose-dependent biomechanical response of tendons following magnetic resonance-guided focused ultrasound (MRgFUS) thermal ablation. METHODS: Ex vivo porcine tendons (n = 72) were embedded in an agar phantom and randomly assigned to 12 groups based on MRgFUS treatment. The treatment time was 10, 20, or 30s, and the applied acoustic power was 25, 50, 75, or 100W. Following each MRgFUS treatment, tendons underwent biomechanical tensile testing on an Instron machine, which calculated stress-strain curves during tendon elongation. Rupture rate, maximum treatment temperature, Young's modulus and ultimate strength were analyzed for each treatment energy. RESULTS: The study revealed a dose-dependent response, with tendons rupturing in over 50% of cases when energy delivery exceeded 1000J and 100% disruption at energy levels beyond 2000J. The achieved temperatures during MRgFUS were directly proportional to energy delivery. The highest recorded temperature was 56.8°C ± 9.34 (3000J), while the lowest recorded temperate was 18.6°C ± 0.6 (control). The Young's modulus was highest in the control group (47.3 MPa ± 6.5) and lowest in the 3000J group (13.2 MPa ± 5.9). There was no statistically significant difference in ultimate strength between treatment groups. CONCLUSION: This study establishes crucial thresholds for reliable and repeatable disruption of tendons, laying the groundwork for future in vivo optimization. The findings prompt further exploration of MRgFUS as a non-invasive modality for tendon disruption, offering hope for improved outcomes in patients with musculotendinous contractures.

Noninvasive magnetic resonance-guided focused ultrasound for tendon disruption: an in vivo Animal study.

PURPOSE: 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.

Prediction of persistent ventricular dilation by initial ventriculomegaly and clot volume in a porcine model.

OBJECTIVE: While intraventricular hemorrhage (IVH) is associated with posthemorrhagic ventricular dilation (PHVD), not all infants affected by high-grade IVH develop PHVD. The authors aimed to determine clot-associated predictors of PHVD in a porcine model by varying the amount and rate of direct intraventricular injection of whole autologous blood. METHODS: Seven 1-week-old piglets underwent craniectomy and injection of autologous blood into the right lateral ventricle. They survived for a maximum of 28 days. MRI was performed prior to injection, immediately postoperatively, and every 7 days thereafter. T1-weighted, T2-weighted, and susceptibility-weighted imaging (SWI) sequences were used to segment ventricular and clot volumes. Spearman correlations were used to determine the relationship between blood and clot volumes and ventricular volumes over time. RESULTS: The maximum ventricular volume was up to 12 times that of baseline. One animal developed acute hydrocephalus on day 4. All other animals survived until planned endpoints. The interaction between volume of blood injected and duration of injection was significantly associated with clot volume on the postoperative scan (p = 0.003) but not the amount of blood injected alone (p = 0.38). Initial postoperative and day 7 clot volumes, but not volume of blood injected, were correlated with maximum (p = 0.007 and 0.014) and terminal (p = 0.014 and 0.036) ventricular volumes. Initial postoperative ventricular volume was correlated with maximum and terminal ventricular volume (p = 0.007 and p = 0.014). CONCLUSIONS: Initial postoperative, maximum, and terminal ventricular dilations were associated with the amount of clot formed, rather than the amount of blood injected. This supports the hypothesis that PHVD is determined by clot burden rather than the presence of blood products and allows further testing of early clot lysis to minimize PHVD risk.

Timing of Temporizing Neurosurgical Treatment in Relation to Shunting and Neurodevelopmental Outcomes in Posthemorrhagic Ventricular Dilatation of Prematurity: A Meta-analysis.

OBJECTIVE: To determine the relationship between timing of initiation of temporizing neurosurgical treatment and rates of ventriculoperitoneal shunt (VPS) and neurodevelopmental impairment in premature infants with post-hemorrhagic ventricular dilatation (PHVD). STUDY DESIGN: We searched MEDLINE, EMBASE, CINAHL, Web of Science, the Cochrane Database of Systematic Reviews, and the Cochrane Center Register of Controlled Trials for studies that reported on premature infants with PHVD who underwent a temporizing neurosurgical procedure. The timing of the temporizing neurosurgical procedure, gestational age, birth weight, outcomes of conversion to VPS, moderate-to-severe neurodevelopmental impairment, infection, temporizing neurosurgical procedure revision, and death at discharge were extracted. RESULTS: Sixty-two full-length articles and 6 conference abstracts (n = 2533 patients) published through November 2020 were included. Pooled rate for conversion to VPS was 60.5% (95% CI, 54.9-65.8), moderate-severe neurodevelopmental impairment 34.8% (95% CI, 27.4-42.9), infection 8.2% (95% CI, 6.7-10.1), revision 14.6% (95% CI, 10.4-20.1), and death 12.9% (95% CI, 10.2-16.4). The average age at temporizing neurosurgical procedure was 24.2 ± 11.3 days. On meta-regression, older age at temporizing neurosurgical procedure was a predictor of conversion to VPS (P < .001) and neurodevelopmental impairment (P < .01). Later year of publication predicted increased survival (P < .01) and external ventricular drains were associated with more revisions (P = .001). Tests for heterogeneity reached significance for all outcomes and a qualitative review showed heterogeneity in the study inclusion and diagnosis criteria for PHVD and initiation of temporizing neurosurgical procedure. CONCLUSIONS: Later timing of temporizing neurosurgical procedure predicted higher rates of conversion to VPS and moderate-severe neurodevelopmental impairment. Outcomes were often reported relative to the number of patients who underwent a temporizing neurosurgical procedure and the criteria for study inclusion and the initiation of temporizing neurosurgical procedure varied across institutions. There is need for more comprehensive outcome reporting that includes all infants with PHVD regardless of treatment.

Establishing Safe Zones to Avoid Nerve Injury in the Approach to the Humerus in Pediatric Patients: A Magnetic Resonance Imaging Study.

BACKGROUND: The surgical anatomy of upper-extremity peripheral nerves in adults has been well described as "safe zones" or specific distances from osseous landmarks. In pediatrics, relationships between nerves and osseous landmarks remain ambiguous. The goal of our study was to develop a model to accurately predict the location of the radial and axillary nerves in children to avoid iatrogenic injury when approaching the humerus in this population. METHODS: We conducted a retrospective review of 116 magnetic resonance imaging (MRI) scans of entire humeri of skeletally immature patients; 53 of these studies met our inclusion criteria. Two independent observers reviewed all scans. Arm length was measured as the distance between the lateral aspect of the acromion and the lateral epicondyle. We then calculated the distances (defined as the percentage of arm length) between the radial nerve and distal osseous landmarks (the medial epicondyle, transepicondylar line, and lateral epicondyle) as well between the axillary nerve and the most lateral aspect of the acromion. RESULTS: The axillary nerve was identified at a distance equaling 18.6% (95% confidence interval [CI], ±0.62%) of arm length inferior to the lateral edge of the acromion. The radial nerve crossed (1) the medial cortex of the posterior part of the humerus at a distance equaling 63.19% (95% CI: ±0.942%) of arm length proximal to the medial epicondyle, (2) the middle of the posterior part of the humerus at a distance equaling 53.9% (95% CI: ±1.08%) of arm length proximal to the transepicondylar line, (3) the lateral cortex of the posterior part of the humerus at a distance equaling 45% (95% CI: ±0.99%) of arm length proximal to the lateral epicondyle, and (4) from the posterior to the anterior compartment at a distance equaling 35.3% (95% CI: ±0.92%) of arm length proximal to the lateral epicondyle. A strong linear relationship between these distances and arm length was observed, with an intraclass correlation coefficient of >0.9 across all measurements. CONCLUSIONS: The positions of the radial and axillary nerves maintain linear relationships with arm lengths in growing children. The locations of these nerves in relation to palpable osseous landmarks are predictable. CLINICAL RELEVANCE: Knowing the locations of upper-extremity peripheral nerves as a proportion of arm length in skeletally immature patients may help to avoid iatrogenic injuries during surgical approaches to the humerus.