Intense Therapeutic Ultrasound for Treatment of Chronic Plantar Fasciitis: A Pivotal Study Exploring Efficacy, Safety, and Patient Tolerance.

Intense therapeutic ultrasound for chronic plantar fasciitis musculoskeletal tissue pain reduction was evaluated in a pivotal clinical trial examining effectiveness, safety, and patient tolerance. In this single-blinded study, 33 patients received 2 treatments that were 4 weeks apart on plantar fascia tissue along with conservative standard of care. Patients were followed for up to 6 months after the first treatment, receiving a physical examination and diagnostic ultrasound at each follow-up visit and completing patient-/subject-reported outcome measure and Foot Function Index surveys. The goal was to reduce overall pain by ≥25% on average and >25% individually. Hypoechoic area changes on diagnostic ultrasound and adverse events were measured. The percentage meeting pain reduction criteria at weeks 4, 8, 12, and 26 were 72%, 81%, 86%, and 79%, respectively. Mean pain scores at each visit were significantly different from baseline (p < .001) at -39%, -49%, -51%, and -44%. Hypoechoic lesions were found in all patients and decreased in size significantly (p < .05) at weeks 8 and 12 (-56% and -67%). Foot Function Index scores declined favorably from baseline (p < .001) at all time points (-32%, -46%, -49%, and -32%). The percentages of patients meeting satisfaction criteria were 72%, 85%, 90%, and 83%. The mean pain score during treatment 1 was 3.4, and during treatment 2, 2.9. Attrition of only 1 patient owing to pain occurred, after treatment 1. No adverse events occurred. Intense therapeutic ultrasound for chronic plantar fasciitis is shown to be effective, safe, and well tolerated in this pivotal clinical trial.

Intense Therapeutic Ultrasound for Pain Relief in the Treatment for Chronic Plantar Fasciopathy.

BACKGROUND: Intense therapeutic ultrasound (ITU) is an innovative ultrasound-based therapy where sound waves are concentrated into select musculoskeletal tissue. These focused waves generate thermal coagula at a controlled depth and space while preserving surrounding tissues. A multicenter study was conducted evaluating the efficiency, safety, and patient tolerance of ITU for the treatment of chronic plantar fasciitis (CPF) pain. METHODS: Seventy-four CPF patients, having failed conservative and/or minimally invasive treatment, participated in the study. Randomized participants either received 2 ITU treatments or 2 sham ITU treatments in addition to standard-of-care therapy. Plantar fascia pain was assessed pretreatment and at 4, 8, 12, and 26 weeks after treatment. Diagnostic ultrasonographic images were analyzed to examine hypoechoic, perifascial lesions whose volumes were calculated until week 12. Function and patient satisfaction were measured using self-reported outcome measures. RESULTS: The treated group reported significant average pain reduction (-26%, -33%, -43%) and hypoechoic lesion volume (-33%, -53%, -68%) at weeks 4, 8, and 12 compared to baseline. Although the control/sham group reported insignificant pain changes at the same time points (-5%, +8%, and +2%) and increased hypoechoic lesion volume (+15%, +28%, +58%). Treated patients reported a significant increase in daily living activities (+28%, +42%, +47%, +40%) compared to the sham/control group (+0.12%, +12%, +3%, +21%). Patient satisfaction remained more than 80% at weeks 8, 12, and 26 for all treatment groups. CONCLUSION: ITU is an effective pain relief treatment for CPF, which is refractory to either conservative measures or minimally invasive treatments. LEVEL OF EVIDENCE: Level II.

Intense focused ultrasound: evaluation of a new treatment modality for precise microcoagulation within the skin.

BACKGROUND AND OBJECTIVE: Focused ultrasound can produce thermal and/or mechanical effects deep within tissue. We investigated the capability of intense focused ultrasound to induce precise and predictable subepidermal thermal damage in human skin. MATERIALS AND METHODS: Postmortem human skin samples were exposed to a range of focused ultrasound pulses, using a prototype device (Ulthera Inc.) emitting up to 45 W at 7.5 MHz with a nominal focal distance of 4.2 mm from the transducer membrane. Exposure pulse duration ranged from 50 to 200 ms. Thermal damage was confirmed by light microscopy using a nitroblue tetrazolium chloride assay, as well as by loss of collagen birefringence in frozen sections. Results were compared with a computational model of intense ultrasound propagation and heating in tissue. RESULTS: Depth and extent of thermal damage were determined by treatment exposure parameters (source power, exposure time, and focal depth). It was possible to create individual and highly confined lesions or thermal damage up to a depth of 4 mm within the dermis. Thermal lesions typically had an inverted cone shape. A precise pattern of individual lesions was achieved in the deep dermis by applying the probe sequentially at different exposure locations. DISCUSSION AND CONCLUSION: Intense focused ultrasound can be used as a noninvasive method for spatially confined heating and coagulation within the skin or its underlying structures. These findings have a significant potential for the development of novel, noninvasive treatment devices in dermatology.

Retrospective Analysis of Plantar Fascia by Ultrasound Imaging in Patients with Plantar Fasciitis.

BACKGROUND: We compared diagnostic ultrasound images of the plantar fascia with available patient histories for symptomatic patients previously diagnosed as having plantar fasciitis. Plantar fascia thickness and depth, the prevalence of perifascial hypoechoic lesions, and injury timelines in patients were reviewed. METHODS: Images and histories for 126 symptomatic patients were collected from a patient database. We documented plantar fascia depth and thickness and the visualization of hypoechoic perifascial lesions. After image analysis, the obtained plantar fascia thickness measurements were compared with various patient attributes for possible relationships, including age, weight, and body mass index. In addition, plantar fascia thickness measurements were separated based on injury timeline as well as symptomatic/asymptomatic foot for patients with unilateral conditions to check for significant differences between subgroups. These were, in turn, compared with a control group of 71 individuals with no heel pain or diagnosis of plantar fasciitis. RESULTS: Overall, mean ± SD symptomatic thickness (n = 148) was 6.53 ± 1.56 mm. Mean ± SD symptomatic depth (n = 136) was 13.36 ± 2.14 mm. For the control group, mean ± SD thickness was 3.20 ± 0.66 mm and depth was 10.30 ± 2.00 mm. Comparison of thickness based on injury timeline showed two significant differences: acute injuries (≤3 months) are significantly thicker than chronic injuries (>3 months), and only acute symptomatic thicknesses are significantly different from their asymptomatic thickness counterparts. Age, weight, and body mass index did not show significant correlations to thickness. Analysis of ultrasound images showed that 93% of symptomatic feet had hypoechoic lesions. CONCLUSIONS: Injury timeline and the presence of hypoechoic lesions may play important roles in patient discomfort, diagnosis, and treatment of plantar fasciitis.

Selective creation of thermal injury zones in the superficial musculoaponeurotic system using intense ultrasound therapy: a new target for noninvasive facial rejuvenation.

OBJECTIVES: To transcutaneously deliver intense ultrasound (IUS) energy to target the facial superficial musculoaponeurotic system (SMAS), to produce discrete thermal injury zones (TIZs) in the SMAS, and to demonstrate the relative sparing of adjacent nontargeted layers superficial and deep to the SMAS layer. METHODS: In 6 unfixed human cadaveric specimens, the SMAS layer was visualized and targeted using the ultrasound imaging component of the IUS device. Using 2 IUS handpieces, 202 exposure lines were delivered bilaterally in multiple facial regions by varying combinations of power and exposure time (0.5-8.0 J). Tissue was then excised and examined grossly and histologically for evidence of thermal injury using nitroblue tetrazolium chloride viability stain. RESULTS: Reproducible TIZs were produced selectively in the SMAS at depths of up to 7.8 mm, and sparing of surrounding tissue including the epidermis. Higher energy settings and high-density exposure line pattern produced a greater degree of tissue shrinkage. CONCLUSIONS: In human cadaveric facial tissue, IUS can noninvasively target and selectively produce TIZs of reproducible location, size, and geometry in the SMAS layer. The ability to produce focused thermal collagen denaturation in the SMAS to induce shrinkage and tissue tightening has not been previously reported and has significant implications for aesthetic facial rejuvenation.

Clinical pilot study of intense ultrasound therapy to deep dermal facial skin and subcutaneous tissues.

OBJECTIVE: To evaluate the clinical safety of intense ultrasound in the treatment of the dermis and subcutaneous tissues of the face and neck in terms of skin inflammation, pain, adverse events, and histologic features. DESIGN: In an open-label, phase 1 study, patients scheduled to undergo a rhytidectomy were enrolled into immediate (face-lift surgery within 24 hours of intense ultrasound treatment) and delayed (face-lift surgery 4-12 weeks after treatment) treatment groups. Intense ultrasound treatments were performed as a series of several linear exposures delivered 1.5 to 2.0 mm apart with the use of 1 of 3 available handpieces with different focal depths. Subject pain ratings and standardized digital photographs were obtained at uniform points. Photographs were blindly rated for inflammation. Histologic evaluation of treated tissues was performed with nitroblue tetrazolium chloride viability stain. RESULTS: Fifteen subjects with a mean +/- SD age of 53 +/- 7 years were enrolled. Seven subjects were nonrandomly assigned to the immediate group and 8 were in the delayed group. On histologic examination, thermal injury zones were consistently identified in the dermis at exposure levels greater than 0.5 J as focal areas of denatured collagen. At this threshold level or above, most patient exposures were associated with transient superficial skin erythema and slight to mild discomfort on a standardized pain scale. No other adverse effects were noted in any case. Thermal injury zones were produced in the expected linear pattern and were consistent in size and depth from zone to zone. Increasing source power did not increase the depth of the epicenter of the thermal injury zone. Epidermis was spared in all cases. CONCLUSION: In this first clinical study of intense ultrasound therapy to facial tissues, the intense ultrasound system allowed for the safe and well-tolerated placement of targeted, precise, and consistent thermal injury zones in the dermis and subcutaneous tissues with sparing of the epidermis.

Miniaturized ultrasound arrays for interstitial ablation and imaging.

A potential alternative to extracorporeal, noninvasive HIFU therapy is minimally invasive intense ultrasound ablation that can be performed laparoscopically or percutaneously. An approach to minimally invasive ablation of soft tissue using miniaturized linear ultrasound arrays is presented here. Recently developed 32-element arrays with aperture 2.3 x 49 mm, therapy frequency 3.1 MHz, pulse-echo bandwidths >42% and surface acoustic energy density >80 W/cm2, are described. These arrays are integrated into a probe assembly, including a coupling balloon and piercing tip, suitable for interstitial ablation. An integrated electronic control system allows therapy planning and automated treatment guided by real-time interstitial B-scan imaging. Image quality, challenging because of limited probe dimensions and channel count, is aided by signal processing techniques that improve image definition and contrast, resulting in image quality comparable to typical transabdominal ultrasound imaging. Ablation results from ex vivo and in vivo experiments on mammalian liver tissue show that this approach is capable of ablation rates and volumes relevant to clinical applications of soft tissue ablation such as treatment of liver cancer.

Treatment of rabbit liver cancer in vivo using miniaturized image-ablate ultrasound arrays.

In the preclinical studies reported here, VX2 cancer within rabbit liver has been treated by bulk ultrasound ablation employing miniaturized image-ablate arrays. Array probes were constructed with 32 elements in a 2.3 × 20 mm(2) aperture, packaged within a 3.1 mm stainless steel tube with a cooling and coupling balloon for in vivo use. The probes were measured capable of 50% fractional bandwidth for pulse-echo imaging (center frequency 4.4 MHz) with >110 W/cm(2) surface intensity available at sonication frequencies 3.5 and 4.8 MHz. B-scan imaging performance of the arrays was measured to be comparable to larger diagnostic linear arrays, although nearfield image quality was reduced by ringdown artifacts. A series of in vivo ablation procedures was performed using an unfocused 32-element aperture firing at 4.8 MHz with exposure durations 20-70.5 s and in situ spatial average, temporal average intensities 22.4-38.5 W/cm(2). Ablation of a complete tumor cross-section was confirmed by vital staining in seven of 12 exposures, with four exposures ablating an additional margin >1 mm beyond the tumor in all directions. Analysis suggests a threshold ablation effect, with complete ablation of tumor cross-sections for exposures with delivery of >838 J acoustic energy. The results show feasibility for in vivo liver cancer ablation using miniaturized image-ablate arrays suitable for interstitial deployment.

Selective transcutaneous delivery of energy to porcine soft tissues using Intense Ultrasound (IUS).

OBJECTIVE: Various energy delivery systems have been utilized to treat superficial rhytids in the aging face. The Intense Ultrasound System (IUS) is a novel modality capable of transcutaneously delivering controlled thermal energy at various depths while sparing the overlying tissues. The purpose of this feasibility study was to evaluate the response of porcine tissues to various IUS energy source conditions. Further evaluation was performed of the built-in imaging capabilities of the device. MATERIALS AND METHODS: Simulations were performed on ex vivo porcine tissues to estimate the thermal dose distribution in tissues after IUS exposures to determine the unique source settings that would produce thermal injury zones (TIZs) at given depths. Exposures were performed at escalating power settings and different exposure times (in the range of 1-7.6 J) using three IUS handpieces with unique frequencies and focal depths. Ultrasound imaging was performed before and after IUS exposures to detect changes in tissue consistency. Porcine tissues were examined using nitro-blue tetrazolium chloride (NBTC) staining sensitive for thermal lesions, both grossly and histologically. The dimensions and depth of the TIZs were measured from digital photographs and compared. RESULTS: IUS can reliably achieve discrete, TIZ at various depths within tissue without surface disruption. Changes in the TIZ dimensions and shape were observed as source settings were varied. As the source energy was increased, the thermal lesions became larger by growing proximally towards the tissue surface. Maximum lesion depth closely approximated the pre-set focal depth of a given handpiece. Ultrasound imaging detected well-demarcated TIZ at depths within the porcine muscle tissue. CONCLUSION: This study demonstrates the response of porcine tissue to various energy dose levels of Intense Ultrasound. Further study, especially on human facial tissue, is necessary in order to understand the utility of this modality in treating the aging face and potentially, other cosmetic applications.

Bulk ablation of soft tissue with intense ultrasound: modeling and experiments.

Methods for the bulk ablation of soft tissue using intense ultrasound, with potential applications in the thermal treatment of focal tumors, are presented. An approximate analytic model for bulk ablation predicts the progress of ablation based on tissue properties, spatially averaged ultrasonic heat deposition, and perfusion. The approximate model allows the prediction of threshold acoustic powers required for ablation in vivo as well as the comparison of cases with different starting temperatures and perfusion characteristics, such as typical in vivo and ex vivo experiments. In a full three-dimensional numerical model, heat deposition from array transducers is computed using the Fresnel approximation and heat transfer in tissue is computed by finite differences, accounting for heating changes caused by boiling and thermal dose-dependent absorption. Similar ablation trends due to perfusion effects are predicted by both the simple analytic model and the full numerical model. Comparisons with experimental results show the efficacy of both models in predicting tissue ablation effects. Phenomena illustrated by the simulations and experiments include power thresholds for in vivo ablation, differences between in vivo and ex vivo lesioning for comparable source conditions, the effect of tissue boiling and absorption changes on ablation depth, and the performance of a continuous rotational scanning method suitable for interstitial bulk ablation of soft tissue.