Is Post-Burn Scarring a Research Priority?

National and international research budgets are insufficient to approve all requests for funding, even if a methodology is of high quality and the outputs are likely to have an impact on improving patient outcomes [...

The effect of injected dose on localized tumor accumulation and cardiac uptake of doxorubicin in a Vx2 rabbit tumor model using MR-HIFU mild hyperthermia and thermosensitive liposomes

Purpose When doxorubicin (DOX) is administered via lyso-thermosensitive liposomes (LTLD), mild hyperthermia enhances localized delivery to heated vs. unheated tumors. The optimal LTLD dose and the impact of different doses on systemic drug distribution are unknown. Materials and methods: In this study, we evaluated local and systemic DOX delivery with three LTLD doses (0.1, 0.5, and 2.5 mg/kg) in a Vx2 rabbit tumor model. Temporally and spatially accurate controlled hyperthermia was achieved using a clinical MR-HIFU system for the intended heating duration (40 min). Results: DOX concentration in tissues delivered from LTLD combined with MR-HIFU mild hyperthermia are dose-dependent, including heated/unheated tumor, heart, and other healthy organs. Higher DOX accumulation and tumor-to-heart drug concentration ratio, defined as the ratio of DOX delivered into the tumor vs the heart, were observed in heated tumors compared to unheated tumors in all three tested doses. The DOX uptake efficiency for each mg/kg of LTLD injected IV of heated tumor was significantly higher than that of unheated tumor and heart within the tested dose range (0.1-2.5 mg/kg). The DOX uptake for the heart linearly scaled up as a function of dose while that for the heated tumor showed some evidence of saturation at the high dose of 2.5 mg/kg. Conclusions: These results provide guidance on clinical protocol design of hyperthermia-triggered drug delivery

Non-Invasive Targeted Peripheral Nerve Ablation Using 3D MR Neurography and MRI-Guided High-Intensity Focused Ultrasound (MR-HIFU) : Pilot Study in a Swine Model

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 limitations and MR-guided HIFU (MR-HIFU) has been used successfully for other clinical indications. The primary purpose of this study was to evaluate the feasibility of utilizing 3D MR neurography to identify and guide ablation of peripheral nerves using a clinical MR-HIFU system. METHODS: Volumetric MR-HIFU was used to induce lesions in the peripheral nerves of the lower limbs in three pigs. Diffusion-prep MR neurography and T1-weighted images were utilized to identify the target, plan treatment and immediate post-treatment evaluation. For each treatment, one 8 or 12 mm diameter treatment cell was used (sonication duration 20 s and 36 s, power 160-300 W). Peripheral nerves were extracted < 3 hours after treatment. Ablation dimensions were calculated from thermal maps, post-contrast MRI and macroscopy. Histological analysis included standard H&E staining, Masson's trichrome and toluidine blue staining. RESULTS: All targeted peripheral nerves were identifiable on MR neurography and T1-weighted images and could be accurately ablated with a single exposure of focused ultrasound, with peak temperatures of 60.3 to 85.7°C. The lesion dimensions as measured on MR neurography were similar to the lesion dimensions as measured on CE-T1, thermal dose maps, and macroscopy. Histology indicated major hyperacute peripheral nerve damage, mostly confined to the location targeted for ablation. CONCLUSION: Our preliminary results indicate that targeted peripheral nerve ablation is feasible with MR-HIFU. Diffusion-prep 3D MR neurography has potential for guiding therapy procedures where either nerve targeting or avoidance is desired, and may also have potential for post-treatment verification of thermal lesions without contrast injection

Light microscopy images of nerves, H&E staining.

<p><b>A</b> Untreated peripheral nerve at 5x magnification. <b>B</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). <b>C</b> Untreated peripheral nerve 40X detail of axons and Schwann cells. <b>D</b> Treated peripheral nerve 40x detail showing regressive nuclear changes karyolysis (dashed arrow) and pyknosis (arrow) and vacuolization (arrowhead).</p

MR neurography of pig sciatic nerve before (top) and after (bottom) MR-HIFU.

<p>SHINKEI images reconstructed as thick-slab (15 mm) maximum intensity projections in sagittal, axial, and coronal orientations.</p

MR thermometry guidance of HIFU thermal ablation of peripheral nerves.

<p>Temperature maps (top) indicate peak temperature of 82.5°C. Thermal dose maps (bottom) predict lesion size of 12 x 29 mm.</p

MRI evaluation of thermal lesions in peripheral nerve.

<p>Hyperintense region on 3D diffusion-prepared MR neurography (top) corresponds with non-enhancing region on T1 post-contrast image.</p