Thermal ablative treatment of uterine fibroids.

In addition to surgical methods of treating uterine fibroids, numerous non-invasive treatments have been developed. Many of these involve the use of hyperthermia, the heating of tissue by a variety of methods. These include the use of lasers, radiofrequency, microwave energy and high intensity focused ultrasound, guided by both ultrasound and magnetic resonance imaging. In this review we examine the technology behind these treatment modalities and review the current evidence for their use.

Quantifying hepatic steatosis - more than meets the eye.

AIMS: The non-alcoholic fatty liver disease (NAFLD) activity score (NAS) is the histological tool used to assess disease severity based on steatosis, inflammation and hepatocyte ballooning. As steatosis contributes up to three of a potential eight points to NAS, it is important to quantify steatosis accurately. We sought to determine the optimum histological technique for identifying fat in tissue. METHODS AND RESULTS: Using tissue from a mouse model of NAFLD, with validation in human liver biopsies, the percentage steatosis and fat droplet size were assessed in haematoxylin and eosin (H&E)- and Oil Red-O (ORO)-stained sections by light microscopy and digital image analysis (DIA). Results were compared to biochemical tissue triglyceride content and MRI assessment of hepatic lipid content. H&E steatosis assessment correlated poorly with tissue triglyceride concentration. However, ORO DIA exhibited much higher sensitivity and specificity for steatosis and correlated very well with triglyceride concentration in mouse and human liver (R = 0.706, P = 0.001 and R = 0.894, P =0.041, respectively). MRI-based assessment of steatosis was inaccurate. CONCLUSIONS: ORO DIA is the most accurate method for detecting and quantifying steatosis. Although H&E-based NAS remains clinically valid in both clinical research and experimental situations, ORO DIA is a more robust technique to assess liver steatosis accurately for NAS scoring.

Renal artery stenosis: comparative assessment by unenhanced renal artery MRA versus contrast-enhanced MRA.

OBJECTIVES: To evaluate steady-state free precession (SSFP) non-contrast-enhanced MR angiography (Unenhanced-MRA) versus conventional contrast-enhanced MR angiography (CE-MRA) in the detection of renal artery stenosis (RAS). METHODS: Retrospective analysis of 70 consecutive patients referred for suspected RAS, examined by SSFP Unenhanced-MRA and CE-MRA. Image quality, quality of visible renal arterial segments, presence and grade of RAS were evaluated. The Unenhanced-MRA were compared against reference standard CE-MRA results. RESULTS: 149 renal arteries were assessed with 21 haemodynamically significant stenoses (≥ 50% stenosis) demonstrated by CE-MRA. Combined sensitivity and specificity for RAS detection by Unenhanced-MRA was 72.8% and 97.8% respectively. There is substantial correlation for RAS detection between Unenhanced-MRA and CE-MRA with kappa values of between 0.64 and 0.74. There was excellent inter-observer correlation for RAS on Unenhanced-MRA (kappa values 0.82-1.0). CONCLUSIONS: Our study has shown Unenhanced-MRA to be a viable alternative to CE-MRA, yielding images equal in quality without the requirement for gadolinium contrast agents. The sensitivity and specificity for the detection of haemodynamically significant stenoses are comparable to CE-MRA. Potentially, Unenhanced-MRA could be used as an initial investigation to avoid performing CE-MRA in patients with normal renal arteries, however we suggest that its real value will lie in being complementary to CE-MRA.

MR-guided focused ultrasound.

The joining of high-intensity focused ultrasound with high-resolution MR guidance has created a system that can produce tissue destruction deep within solid organs without any invasion. Accurate targeting and thermal mapping are provided by MRI and allow very accurate deposition of energy in tissues that can be altered in response to near real-time thermal imaging produced by MR so that the variation in tissue response that is otherwise observed can be overcome. Current areas of successful application of MR-guided focused ultrasound are described in the treatment of uterine fibroids and other areas of emerging applications in additional solid organs are also discussed.

Robot-assistant for MRI-guided liver ablation: A pilot study.

PURPOSE: Percutaneous ablation under MRI-guidance allows treating otherwise inoperable liver tumors locally using a catheter probe. However, manually placing the probe is an error-prone and time consuming task that requires a considerable amount of training. The aim of this paper was to present a pneumatically actuated robotic instrument that can assist clinicians in MRI-guided percutaneous intervention of the liver and to assess its functionality in a clinical setting. The robot positions a needle-guide inside the MRI scanner bore and assists manual needle insertions outside the bore. METHODS: The robot supports double oblique insertions that are particularly challenging for less experienced clinicians. Additionally, the system employs only standard imaging sequences and can therefore be used on different MRI scanners without requiring prior integration. The repeatability and the accuracy of the robot were evaluated with an optical tracking system. The functionality of the robot was assessed in an initial pilot study on two patients that underwent MRI-guided laser ablation of the liver. RESULTS: The robot positioned the needle-guide in a repeatable manner with a mean error of 0.35 mm and a standard deviation of 0.32 mm. The mean position error corresponding to the needle tip, measured for an equivalent needle length of 195 mm over 25 fixed points, was 2.5 mm with a standard deviation of 1.2 mm. The pilot study confirmed that the robot does not interfere with the equipment used for MRI-guided laser ablation and does not visibly affect the MR images. The robot setup integrated seamlessly within the established clinical workflow. The robot-assisted procedure was successfully completed on two patients, one of which required a complex double oblique insertion. For both patients, the insertion depth and the tumor size were within the range reported for previous MRI-guided percutaneous interventions. A third patient initially enrolled in the pilot study and was considerably heavier than the others, preventing the use of the robot and requiring several freehand insertion attempts. CONCLUSIONS: The robot repeatability and accuracy are appropriate for liver tumors normally treated with MRI-guided ablation. The results of the pilot study endorse the clinical use of the robot in its current form: the robot is fully functional and MRI-compatible in a clinical setting and is suitable for double-oblique needle insertions.

Optothermal profile of an ablation catheter with integrated microcoil for MR-thermometry during Nd:YAG laser interstitial thermal therapies of the liver­an in-vitro experimental and theoretical study.

PURPOSE: Flexible microcoils integrated with ablation catheters can improve the temperature accuracy during local MR-thermometry in Nd:YAG laser interstitial thermal therapies. Here, the authors are concerned with obtaining a preliminary confirmation of the clinical utility of the modified catheter. They investigate whether the thin-film substrate and copper tracks of the printed coil inductor affect the symmetry of the thermal profile, and hence of the lesion produced. METHODS: Transmission spectroscopy in the near infrared was performed to test for the attenuation at 1064 nm through the 25 µm thick Kapton substrate of the microcoil. The radial transmission profile of an infrared high-power, light emitting diode with >80% normalized power at 1064 nm was measured through a cross section of the modified applicator to assess the impact of the copper inductor on the optical profile. The measurements were performed in air, as well as with the applicator surrounded by two types of scattering media; crystals of NaCl and a layer of liver-mimicking gel phantom. A numerical model based on Huygens-Fresnel principle and finite element simulations, using a commercially available package (COMSOL Multiphysics), were employed to compare with the optical measurements. The impact of the modified optical profile on the thermal symmetry was assessed by examining the high resolution microcoil derived thermal maps from a Nd:YAG laser ablation performed on a liver-mimicking gel phantom. RESULTS: Less than 30% attenuation through the Kapton film was verified. Shadowing behind the copper tracks was observed in air and the measured radial irradiation correlated well with the diffraction pattern calculated numerically using the Huygens-Fresnel principle. Both optical experiments and simulations, demonstrate that shadowing is mitigated by the scattering properties of a turbid medium. The microcoil derived thermal maps at the end of a Nd:YAG laser ablation performed on a gel phantom in a 3 T scanner confirm that the modified irradiation pattern does not disrupt the thermal symmetry, even though, unlike tissue, the gel is minimally scattering. CONCLUSIONS: The results from this initial assessment indicate that microcoils can be safely integrated with ablation catheters and ensure that the complete necrosis of the liver tumor can still be achieved.

Safety and treatment volumes achieved following new developments of the magnetic resonance-guided focused ultrasound system in the treatment of uterine fibroids: a cohort study.

BACKGROUND: This research investigates whether modifications to the magnetic resonance-guided focused ultrasound ablation of uterine fibroid (MRgFUS) system used resulted in improved treatment volumes of uterine fibroids, while maintaining safety. METHODS: This study is a prospective cohort analysis of 34 women undergoing the ExAblate 2100 MRgFUS treatment for their uterine fibroids. RESULTS: The percentage of non-perfused volume (NPV) achieved with the ExAblate 2100 system was 54.92% compared with 50.49 % with the ExAblate 2000 system over the preceding year (p = 0.543). The ExAblate 2100 system resulted in a greater NPV in hyper-intense fibroids compared with the ExAblate 200 system (43.20% versus 36.33%, p = 0.005). There have been no recorded hospital admissions, no skins burns, and no reported major adverse events since the introduction of this new system. CONCLUSION: Overall, the new system has thus far shown an encouraging safety record and an improvement in non-perfused volumes achieved, especially in hyper-intense fibroids.

The road to clinical use of high-intensity focused ultrasound for liver cancer: technical and clinical consensus.

Clinical use of high-intensity focused ultrasound (HIFU) under ultrasound or MR guidance as a non-invasive method for treating tumors is rapidly increasing. Tens of thousands of patients have been treated for uterine fibroid, benign prostate hyperplasia, bone metastases, or prostate cancer. Despite the methods' clinical potential, the liver is a particularly challenging organ for HIFU treatment due to the combined effect of respiratory-induced liver motion, partial blocking by the rib cage, and high perfusion/flow. Several technical and clinical solutions have been developed by various groups during the past 15 years to compensate for these problems. A review of current unmet clinical needs is given here, as well as a consensus from a panel of experts about technical and clinical requirements for upcoming pilot and pivotal studies in order to accelerate the development and adoption of focused ultrasound for the treatment of primary and secondary liver cancer.

Midfoot and hindfoot bone marrow edema identified by magnetic resonance imaging in feet of subjects with diabetes and neuropathic ulceration is common but of unknown clinical significance.

OBJECTIVE: We conducted a retrospective cohort study assessing the prevalence and clinical and radiological outcome of remote areas of bone marrow edema on magnetic resonance imaging (MRI) in the feet of subjects with diabetes and neuropathic foot ulceration. RESEARCH DESIGN AND METHODS: MRIs performed over 6 years looking for osteomyelitis associated with neuropathic lesions were assessed for remote areas of signal change. RESULTS: Seventy MRI studies were assessed. Remote areas of signal change were present in 21 (30%) subjects, involved midfoot or hindfoot in 20 subjects, were associated with younger age and renal replacement therapy, and did not predict future Charcot neuroarthropathy or infection at that site. Repeat MRIs in 11 subjects with such areas found that none had progressed, six had improved, and two had resolved; in 29 subjects without such areas, five had developed new areas. CONCLUSIONS: Bone marrow edema in the midfoot and hindfoot of subjects with diabetes and neuropathic lesions is common, often transient, and of unknown significance.

Patient suitability for magnetic resonance guided focused ultrasound surgery of uterine fibroids.

OBJECTIVE: To assess selection criteria used to determine eligibility for magnetic resonance-guided focused ultrasound surgery (MRgFUS) for the treatment of symptomatic uterine fibroids; to assess the percentage of patients suitable for MRgFUS. STUDY DESIGN: A retrospective analysis of 144 patients seeking minimally invasive treatment options for symptomatic uterine fibroids at a single treatment center. Clinical eligibility for MRgFUS was assessed at a gynecology clinic by a Gynecology research fellow trained in the procedure and suitability was assessed by magnetic resonance imaging. Several techniques were used to mitigate against factors that are contra-indications for MRgFUS. RESULTS: 100% of patients interested in MRgFUS were deemed clinically eligible for the procedure and 74% were deemed technically suitable to proceed with treatment. CONCLUSIONS: Mitigation techniques allow for less restrictive MRgFUS selection criteria for treatment for symptomatic uterine fibroids. These less restrictive criteria are expected to expand the pool of patients for whom MRgFUS is a viable treatment option for uterine fibroid symptoms.

Low wall shear stress predicts subsequent development of wall hypertrophy in lower limb bypass grafts.

BACKGROUND: Venous grafts commonly develop myointimal hyperplasia, which can lead to stenoses and, ultimately, with expression of adhesion molecules, lumenal occlusion. The aim of the present study was to investigate whether wall shear stress measured post-operatively would predict subsequent myointimal hypertrophy in lower limb venous bypass grafts. METHODS: Magnetic resonance imaging and ultrasound were performed in a cohort of patients following lower limb venous bypass graft surgery for peripheral arterial disease at baseline (1-2 weeks) and at follow-up (9-12 months). Wall shear stress was determined at baseline using computational fluid dynamics techniques and intima-media thickness along the length of the graft was measured by ultrasound at baseline and follow up. RESULTS: Complete follow-up was possible in eight patients, in whom low wall shear stress at baseline predicted high intima-media thickness. The relationship between wall shear stress (WSS) and intima-media thickness (IMT) was curvilinear with IMT increasing sharply at lower levels of WSS (IMT >1.0 mm at <0.3 Pa). CONCLUSIONS: Low wall shear stress is associated with subsequent increase in myointimal thickness in lower limb venous bypass grafts. This is believed to be the first prospective study in humans to demonstrate the relationship between low wall shear stress and myointimal thickening and indicates a likely causative role for low wall shear stress in the development of myointimal hyperplasia.

Clinical outcomes of focused ultrasound surgery for the treatment of uterine fibroids.

OBJECTIVE: To assess outcomes at 6 and 12 months after magnetic resonance-guided focused ultrasound surgery (MRgFUS) for symptomatic uterine leiomyomas. DESIGN: Multicenter clinical trial. SETTING: Academic medical centers. PATIENT(S): Premenopausal women with symptomatic uterine leiomyomas and no plans for future pregnancy (n = 109 at 6 months and n = 82 at 12 months). INTERVENTION(S): A single treatment session of MRgFUS for uterine fibroids. MAIN OUTCOME MEASURE(S): Reduction in fibroid symptoms as measured by the symptom severity score (SSS) of the Uterine Fibroid Quality-of-Life Instrument (UFS-QOL), the only validated measure of leiomyoma symptomatology. A 10-point reduction in the SSS was selected as the targeted improvement. RESULT(S): Seventy-one percent of women undergoing MRgFUS reached the targeted symptom reduction at 6 months, and 51% reached this at 12 months. The magnitude of improvement in SSS was greater than predicted, with subjects having a mean decrease of 39% and 36% at 6 and 12 months, respectively. This paralleled the improvement seen using the short form-36 instrument. A modest volume reduction similar in magnitude to the treated volume was seen. The incidence of adverse events was low. CONCLUSION(S): MRgFUS treatment results in short-term symptom reduction for women with symptomatic uterine leiomyomas with an excellent safety profile.

Feasibility of abdomino-pelvic T1-weighted real-time thermal mapping of laser ablation.

PURPOSE: To prove the hypothesis that T1-weighted (T1W) thermal mapping is reliable and achievable in magnetic resonance (MR)-guided laser tumor ablation. MATERIALS AND METHODS: Near real-time gray and color-scale T1W thermal maps in 111 MR-guided laser thermal ablations (LTA) of liver, kidney, and uterine tumors were studied. After laser fiber placement, near real-time gray and color-scale thermal maps were produced. Previous work showed T1 signal is inversely proportional to temperature below 55 degrees C (the point of irreversible necrosis). RESULTS: Thermal mapping was successful in 84% of uterine, 74% of hepatic, and 20% of renal ablations. For hepatic and uterine tumors, size and conspicuity of thermal lesions were significantly greater on subtracted colorized images rather than gray-scale raw image mapping (P = 0.001, paired Student's t-test). Patient movement (N = 24), fiber charring N = 2), magnetic field distortion, and reconstruction errors (N = 2) caused mapping failure. For both renal and hepatic tumors, comparison of near real-time T1W colorized thermal map and follow up gadolinium-enhanced MR imaging revealed moderate correlation (Pearson correlation coefficient of 0.55 and 0.5, respectively). CONCLUSION: In hepatic, renal, and uterine thermal maps, the color scale produced significantly greater sized lesions with significantly greater conspicuity than the gray scale. T1W thermal mapping was reliable and successfully achieved in 73.7% of procedures, and predicted the ablated area of the tumor moderately well.

Detection of an occult hepatocellular carcinoma using ultrasound with liver-specific microbubbles.

The radiological surveillance of cirrhosis to detect the development of hepatocellular carcinoma (HCC) is problematic because no highly sensitive and specific imaging investigation is available. Ultrasound is typically the first modality used but is less accurate than other imaging modalities. We report the first case of a patient with cirrhosis in whom US imaging with liver-specific microbubbles detected an HCC prior to its detection by MR. The use of liver-specific microbubble US contrast agents is an exciting development in the detection of HCC in chronic liver disease and may help to rectify some of the shortcomings of US.

Focused ultrasound treatment of uterine fibroid tumors: safety and feasibility of a noninvasive thermoablative technique.

OBJECTIVE: The purpose of this study was to determine the safety and efficacy of focused ultrasound surgery with magnetic resonance imaging guidance for the noninvasive treatment of uterine leiomyomas. STUDY DESIGN: Fifty-five women with clinically significant uterine leiomyomas were treated. Pain and complications were assessed prospectively, and posttreatment magnetic resonance imaging was used to measure the treatment effects. Patients in three of the five centers underwent planned hysterectomy after treatment, which provided pathologic correlation of treatment. RESULTS: Seventy-six percent of the enrolled patients completed the full treatment session. All treatments were conducted in an outpatient setting with minimal discomfort for subjects and no major complications. Pathologic examination of the uterus confirmed that magnetic resonance imaging guidance provides the safe and accurate delivery of effective levels of thermal energy with a 3-fold increase in volume of histologically documented necrosis, compared with treatment volume (6.6 +/- 0.8 vs 18.4 +/- 3.9 mL, P <.005). CONCLUSION: Magnetic resonance imaging-guided focused ultrasound surgery appears to be a well-tolerated treatment for uterine leiomyomas.

MRI guidance of focused ultrasound therapy of uterine fibroids: early results.

OBJECTIVE: The purpose of this study was to explore our hypothesis that MRI-guided focused ultrasound therapy for the treatment of uterine fibroids will lead to a significant reduction in symptoms and improvement in quality of life. We describe focused ultrasound therapy applications and the method for monitoring the thermal energy deposited in the fibroids, including the MRI parameters required, in a prospective review of 108 treatments. MATERIALS AND METHODS: Patients presenting with symptomatic uterine fibroids who attained a minimal symptom severity score and who would otherwise have been offered a hysterectomy were recruited. Thermal lesions were created within target fibroids using an MRI-guided focused ultrasound therapy system. The developing lesion was monitored using real-time MR thermometry, which was used to assess treatment outcome in real time to change treatment parameters and achieve the desired outcome. Fibroid volume, fibroid symptoms, and quality-of-life scores were measured before treatment and 6 months after treatment. Adverse events were actively monitored and recorded. RESULTS: In this study, 79.3% of women who had been treated reported a significant improvement in their uterine fibroid symptoms on follow-up health-related quality-of-life questionnaires, which supports our hypothesis. The mean reduction in fibroid volume at 6 months was 13.5%, but nonenhancing volume (mean, 51 cm(3)) remained within the treated fibroid at 6 months. CONCLUSION: This early description of MRI-guided focused ultrasound therapy treatment of fibroids includes follow-up data and shows that, although the volume reduction is moderate, it correlates with treatment volume and the symptomatic response to this treatment is encouraging.