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Discogenic back pain presents a major public health issue, with current therapeutic interventions limited to short-term symptom relief without providing regenerative remedies for diseased intervertebral discs (IVD). Many of these interventions are invasive and can diminish the biomechanical integrity of the IVDs. Low intensity pulsed ultrasound (LIPUS) is a potential treatment option that is both non-invasive and regenerative. LIPUS has been shown to be a clinically effective method for the enhancement of wound and fracture healing. Recent in vitro studies have shown that LIPUS stimulation induces an upregulation functional matrix proteins and downregulation of inflammatory factors in cultured IVD cells. However, we do not know the effects of LIPUS on an in vivo model for intervertebral disc degeneration. The objective of this study was to show technical feasibility of building a LIPUS system that can target the rat tail IVD and apply this setup to a model for acute IVD degeneration. A LIPUS exposimetry system was built using a 1.0 MHz planar transducer and custom housing. Ex vivo intensity measurements demonstrated LIPUS delivery to the center of the rat tail IVD. Using an established stab-incision model for disc degeneration, LIPUS was applied for 20 minutes daily for five days. For rats that displayed a significant injury response, LIPUS treatment caused significant upregulation of Collagen II and downregulation of Tumor Necrosis Factor – α gene expression. Our preliminary studies indicate technical feasibility of targeted delivery of ultrasound to a rat tail IVD for studies of LIPUS biological effects.

Ultrasound devices are being investigated for endoluminal and intraductal access for targeted thermal ablation or hyperthermia of pancreas under MR guidance and temperature monitoring. Simulations using patient-specific 3D models were developed for applicator design and development of treatment delivery strategies. MR-compatible devices were constructed for endoluminal (3-5 MHz planar or lightly focused rectangular elements, 12-mm OD assembly, expandable balloon), transgastric interstitial and intraductal (6-8 MHz multi-sectored tubular elements, 2-mm catheter) deployment. Micro-coils were integrated for active MR tracking of position and alignment. The proof-of-concept devices were tested in phantoms, ex vivo tissues, cadaveric porcine models, and in vivo animal models under 3T MR temperature imaging (MRTI). Results indicate endoluminal devices could ablate 2-2.5 cm depth from gastric wall for tumors of the pancreatic head, and multi-sectored tubular intraductal and interstitial applicators could ablate 2.3-3.4 cm diameter targets with directional control. Intraductal applicators could produce effective hyperthermia (>40 C) extending 15 mm radial. Customized tracking sequences could be used to locate 3D position of the applicators. Endoluminal, interstitial, and intraductal ultrasound applicators show promise for ablation or hyperthermia of pancreatic tumors. MR guidance can be employed for positioning these devices with active tracking coils and real time temperature monitoring. (NIH-P01CA159992.)

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