37th International Conference of the IEEE Engineering in Medicine and Biology Milan, Italy, August 2015 Intense Therapy Ultrasound (ITU) for the Treatment of Chronic Plantar Fasciitis: Preliminary Results of Clinical Study Michael H. Slayton, Ph.D., Member IEEE1, Richard C. Amodei, RDMS1, Ashley McNelly2 and L. Daniel Latt MD, Ph.D.2, 1- Guided Therapy Systems, Mesa, AZ 2- University of Arizona, School of Medicine, Tucson, AZ

Overview Background Protocol & Methods Results & Discussion Conclusion

Clinical Approach Intense Therapeutic ultrasound (ITU) uses high-frequency high-intensity focused ultrasound to create small thermal injury zones noninvasively inside soft tissue. It has been shown to initiate a tissue repair cascade and promote collagen generation in musculoskeletal tissue. A double blinded, randomized, sham controlled clinical study of the use of ITU for the treatment of chronic plantar fasciitis has been conducted by IRB approved clinical protocol. 24 patients with chronic plantar fasciitis were randomized to receive either ITU treatment with 3.3 MHz high intensity (>5000 w/cm²) ultrasound device or sham control. High frequency ultrasound imaging was used to access the changes in Plantar Fascia and validated patient reported outcome instruments were used to assess changes in heel pain and function.

Protocol/Methods Twenty four patients with chronic (greater than 3 months) heel pain due to plantar fasciitis (PF) were randomized to standard therapy (anti-inflammatory pills, stretching, and gel heel cups) plus ITU (“Treatment”, n=17) or standard therapy plus sham ITU (“control”, n=7) treatment groups. Treatments were performed at enrollment and two weeks later. ITU treatments were delivered using a custom 3.3 MHz therapeutic ultrasound system (Guided Therapy Systems, Mesa, AZ). The treatment consisted of 320 pulses of 4-5 J distributed in 12 lines, with a focal depth of up to 15 mm. Treatment time did not exceed 12 min. ITU placebo consisted of the same number of treatment lines and treatment time with energy delivery set to 0 J. Treatment effect was assessed with diagnostic ultrasound and patient reported outcomes at 2, 4, 6, and 12 weeks after initiating treatment. Diagnostic ultrasound was performed using as 12MHz probe with a high resolution imaging system (Spark, Ardent Sound Inc., Mesa, AZ) by a certified sonographer. Ultrasound images were analyzed to determine the size of lesions around or within the Plantar Fascia. Patient reported outcomes consisted of PROMIS physical function computer adaptive test (PF-CAT) [2], PROMIS global health, Foot Function Index pain subscale, and a non-validated heel pain specific questionnaire. Both the sonographer and the study coordinator administering the patient reported outcome instruments were blinded to group assignment. P Values calculated via 2-tailed paired T-test for both treatment and sham groups for lesion volume and Foot Function Index Pain Subscale comparison.

Results/Discussion The size and calculated volumes of hypoechoic perifascial lesions were measured by using high resolution imaging systems and results are shown in Fig. 1 for “Treated” group (n=17) and for “Sham” group (n=7). A significant difference in patient reported outcome scores was also found for FFI pain subscale (Fig 3), improvement in pain and satisfaction with treatment. Results of the heel pain assessment were obtained by PROMIS validated survey and generated by NIH validated REDCap software. Fig. 2 summarizes the “Treat” group (n=17) results for heel pain over the 12 weeks follow-up period. “Control” group (n=7) demonstrated “No change or Worse” results 12 weeks after baseline assessment. Patient satisfaction results in the Treatment group with 100% satisfaction are shown in Fig. 4. Sham group showed 25% satisfaction (graph not shown)

Fig.1: Comparison Perifascial Lesion Volume by Week and Visit Treatment vs. Sham Treatment Subjects Treatment, P <0.001 Visits 3,4 and 5 Sham Treatment, P >0.25 for all visits

Fig. 2: Comparison of Subjective Heel Pain by Visit (12 weeks)

Fig. 3: Patient reported heel pain by visit (± Standard Error)

Fig. 4: Self-reported patient satisfaction with the treatment results for Treatment group.

Baseline & Treatment 1 2 Weeks after Treatment 2 10 Weeks after Treatment 2 Figure X: Diagnostic Ultrasound Images of Treated Subject Perifascial Lesion Volume Reductions noted from Baseline to 12 Weeks

Baseline & Treatment 1 4 Weeks after Treatment 2 10 Weeks after Treatment 2 Figure X: Diagnostic Ultrasound Images of Treated Subject Perifascial Lesion Volume Reductions noted from Baseline to 12 Weeks

Conclusions Preliminary results of this clinical study using noninvasive ITU for the treatment of chronic PF showed statistically significant improvement for ITU treatment as compared to sham control in size of perifascial lesions, reduction in heel pain, and satisfaction with treatment at 12 weeks follow-up. Perifascial lesions measured by high frequency diagnostic ultrasound were reduced on the average by 80% by 10 weeks from the 2nd treatment and patient reported outcomes showed statistically significant reduction of pain in Treated group vs Sham group with 100% satisfaction in Treated group. The study is ongoing and will help to both confirm and add detail to these preliminary findings.