In this randomized, sham-controlled trial, MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor who had not had a response to medication. Adverse effects of ...the procedure included sensory deficits and gait disturbances.
Essential tremor, the most common movement disorder,
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is characterized by a distinctive postural and intention tremor typically affecting the hands more than the legs, trunk, head, or voice.
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Essential tremor does not shorten life expectancy, but it can affect quality of life, functional activities, mood, and socialization.
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Class I evidence exists for propranolol and primidone as first-line medications that reduce tremor by approximately 60% in 50% of patients.
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If resistance to medications develops or side effects are unacceptable, neurosurgical intervention is considered, primarily targeting the nucleus ventralis intermedius of the thalamus, a component of tremor circuitry that . . .
Objective: Low-frequency low-intensity pulsed ultrasound (LIPUS) has emerged as a non-invasive neuromodulation tool. The aim of this study is to examine whether LIPUS stimulation of the motor cortex ...can improve parkinsonian motor deficit in a mouse model induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Methods: Acute Parkinson's disease (PD) mouse model is built by injection of MPTP (20 mg/kg) every 4 h in a total of four doses in one day. Mice are randomized into control, MPTP, sham-LIPUS+MPTP, and LIPUS+MPTP group. For LIPUS+MPTP group, 7 days of LIPUS (800 kHz, 10% duty cycle, 100-Hz pulse repetition frequency, 40 min/day) is delivered to the motor cortex. An open field test (OFT) is conducted on day 4 and a pole test on day 5, respectively. Striatal total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) are measured on day 8. The safety of LIPUS is verified using Hematoxylin and esosin (HE) staining and Nissl staining. Results: LIPUS treatment improves rearing number in the OFT on day 4 (n = 8, p = 0.037) and locomotor activity in the pole test on day 5 (n = 8, p = 0.007) compared with the sham-LIPUS+MPTP group. Moreover, LIPUS increases T-SOD (n = 7, p = 0.006) and GSH-PX (n = 7, p = 0.030) compared with the sham-LIPUS+MPTP group. In addition, HE and Nissl staining shows no brain tissue injury induced by LIPUS. Conclusion: These findings demonstrate that LIPUS may have neuromodulation effects in PD mice. Significance: LIPUS may provide a novel neuromodulation tool for PD treatment.
Ultrasound (US) is widely known for its utility as a biomedical imaging modality. An abundance of evidence has recently accumulated showing that US is also useful for non-invasively modulating brain ...circuit activity. Through a series of studies discussed in this short review, it has recently become recognized that transcranial focused ultrasound can exert mechanical (non-thermal) bioeffects on neurons and cells to produce focal changes in the activity of brain circuits. In addition to highlighting scientific breakthroughs and observations that have driven the development of the field of ultrasonic neuromodulation, this study also provides a discussion of mechanisms of action underlying the ability of ultrasound to physically stimulate and modulate brain circuit activity. Exemplifying some forward-looking tools that can be developed by integrating ultrasonic neuromodulation with other advanced acoustic technologies, some innovative acoustic imaging, beam forming, and focusing techniques are briefly reviewed. Finally, the future outlook for ultrasonic neuromodulation is discussed, specifically in the context of applications employing transcranial focused ultrasound for the investigation, diagnosis, and treatment of neuropsychiatric disorders.
IMPORTANCE: Clinical trials have confirmed the efficacy of focused ultrasound (FUS) thalamotomy in essential tremor, but its effectiveness and safety for managing tremor-dominant Parkinson disease ...(TDPD) is unknown. OBJECTIVE: To assess safety and efficacy at 12-month follow-up, accounting for placebo response, of unilateral FUS thalamotomy for patients with TDPD. DESIGN, SETTING, AND PARTICIPANTS: Of the 326 patients identified from an in-house database, 53 patients consented to be screened. Twenty-six were ineligible, and 27 were randomized (2:1) to FUS thalamotomy or a sham procedure at 2 centers from October18, 2012, to January 8, 2015. The most common reasons for disqualification were withdrawal (8 persons 31%), and not being medication refractory (8 persons 31%). Data were analyzed using intention-to-treat analysis, and assessments were double-blinded through the primary outcome. INTERVENTIONS: Twenty patients were randomized to unilateral FUS thalamotomy, and 7 to sham procedure. The sham group was offered open-label treatment after unblinding. MAIN OUTCOMES AND MEASURES: The predefined primary outcomes were safety and difference in improvement between groups at 3 months in the on-medication treated hand tremor subscore from the Clinical Rating Scale for Tremor (CRST). Secondary outcomes included descriptive results of Unified Parkinson’s Disease Rating Scale (UPDRS) scores and quality of life measures. RESULTS: Of the 27 patients, 26 (96%) were male and the median age was 67.8 years (interquartile range IQR, 62.1-73.8 years). On-medication median tremor scores improved 62% (IQR, 22%-79%) from a baseline of 17 points (IQR, 10.5-27.5) following FUS thalamotomy and 22% (IQR, −11% to 29%) from a baseline of 23 points (IQR, 14.0-27.0) after sham procedures; the between-group difference was significant (Wilcoxon P = .04). On-medication median UPDRS motor scores improved 8 points (IQR, 0.5-11.0) from a baseline of 23 points (IQR, 15.5-34.0) following FUS thalamotomy and 1 point (IQR, −5.0 to 9.0) from a baseline of 25 points (IQR, 15.0-33.0) after sham procedures. Early in the study, heating of the internal capsule resulted in 2 cases (8%) of mild hemiparesis, which improved and prompted monitoring of an additional axis during magnetic resonance thermometry. Other persistent adverse events were orofacial paresthesia (4 events 20%), finger paresthesia (1 event 5%), and ataxia (1 event 5%). CONCLUSIONS AND RELEVANCE: Focused ultrasound thalamotomy for patients with TDPD demonstrated improvements in medication-refractory tremor by CRST assessments, even in the setting of a placebo response. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01772693
Ultrasound (US)-triggered sonodynamic therapy (SDT) that enables noninvasive treatment of large internal tumors has attracted widespread interest. For improvement in the therapeutic responses to SDT, ...more effective and stable sonosensitizers are still required. Herein, ultrafine titanium monoxide nanorods (TiO1+x NRs) with greatly improved sono-sensitization and Fenton-like catalytic activity were fabricated and used for enhanced SDT. TiO1+x NRs with an ultrafine rodlike structure were successfully prepared and then modified with polyethylene glycol (PEG). Compared to the conventional sonosensitizer, TiO2 nanoparticles, the PEG–TiO1+x NRs resulted in much more efficient US-induced generation of reactive oxygen species (ROS) because of the oxygen-deficient structure of TiO1+x NR, which predominantly serves as the charge trap to limit the recombination of US-triggered electron–hole pairs. Interestingly, PEG–TiO1+x NRs also exhibit horseradish-peroxidase-like nanozyme activity and can produce hydroxyl radicals (•OH) from endogenous H2O2 in the tumor to enable chemodynamic therapy (CDT). Because of their efficient passive retention in tumors post intravenous injection, PEG–TiO1+x NRs can be used as a sonosensitizer and CDT agent for highly effective tumor ablation under US treatment. In addition, no significant long-term toxicity of PEG–TiO1+x NRs was found for the treated mice. This work highlights a new type of titanium-based nanostructure with great performance for tumor SDT.
Therapeutic ultrasound for venous leg ulcers Cullum, Nicky; Liu, Zhenmi; Cullum, Nicky
Cochrane database of systematic reviews,
05/2017, Letnik:
2017, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Background
Venous leg ulcers are a type of chronic, recurring, complex wound that is more common in people aged over 65 years. Venous ulcers pose a significant burden to patients and healthcare ...systems. While compression therapy (such as bandages or stockings) is an effective first‐line treatment, ultrasound may have a role to play in healing venous ulcers.
Objectives
To determine whether venous leg ulcers treated with ultrasound heal more quickly than those not treated with ultrasound.
Search methods
We searched the Cochrane Wounds Specialised Register (searched 19 September 2016); the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library 2016, Issue 8); Ovid MEDLINE (including In‐Process & Other Non‐Indexed Citations, MEDLINE Daily and Epub Ahead of Print) (1946 to 19 September 2016); Ovid Embase (1974 to 19 September 2016); and EBSCO CINAHL Plus (1937 to 19 September 2016). We also searched three clinical trials registries and the references of included studies and relevant systematic reviews. There were no restrictions based on language, date of publication or study setting.
Selection criteria
Randomised controlled trials (RCTs) that compared ultrasound with no ultrasound. Eligible non‐ultrasound comparator treatments included usual care, sham ultrasound and alternative leg ulcer treatments.
Data collection and analysis
Two authors independently assessed the search results and selected eligible studies. Details from included studies were summarised using a data extraction sheet, and double‐checked. We attempted to contact trial authors for missing data.
Main results
Eleven trials are included in this update; 10 of these we judged to be at an unclear or high risk of bias. The trials were clinically heterogeneous with differences in duration of follow‐up, and ultrasound regimens. Nine trials evaluated high frequency ultrasound; seven studies provided data for ulcers healed and two provided data on change in ulcer size only. Two trials evaluated low frequency ultrasound and both reported ulcers healed data.
It is uncertain whether high frequency ultrasound affects the proportion of ulcers healed compared with no ultrasound at any of the time points evaluated: at seven to eight weeks (RR 1.21, 95% CI 0.86 to 1.71; 6 trials, 678 participants; low quality evidence ‐ downgraded once for risk of bias and once for imprecision); at 12 weeks (RR 1.26, 95% CI 0.92 to 1.73; 3 trials, 489 participants; moderate quality evidence ‐ downgraded once for imprecision); and at 12 months (RR 0.93, 95% CI 0.73 to 1.18; 1 trial, 337 participants; low quality evidence ‐ downgraded once for unclear risk of bias and once for imprecision).
One trial (92 participants) reported that a greater percentage reduction in ulcer area was achieved at four weeks with high‐frequency ultrasound, while another (73 participants) reported no clear difference in change in ulcer size at seven weeks. We downgraded the level of this evidence to very low, mainly for risk of bias (typically lack of blinded outcome assessment and attrition) and imprecision.
Data from one trial (337 participants) suggest that high frequency ultrasound may increase the risk of non‐serious adverse events (RR 1.29, 95% CI 1.02 to 1.64; moderate quality evidence ‐ downgraded once for imprecision) and serious adverse events (RR 1.21, 95% CI 0.78 to 1.89; moderate quality evidence downgraded once for imprecision).
It is uncertain whether low frequency ultrasound affects venous ulcer healing at eight and 12 weeks (RR 3.91, 95% CI 0.47 to 32.85; 2 trials, 61 participants; very low quality evidence (downgraded for risk of bias and imprecision)).
High‐frequency ultrasound probably makes little or no difference to quality of life (moderate quality evidence, downgraded for imprecision). The outcomes of adverse effects, quality of life and cost were not reported for low‐frequency ultrasound treatment.
Authors' conclusions
It is uncertain whether therapeutic ultrasound (either high or low frequency) improves the healing of venous leg ulcers. We rated most of the evidence as low or very low quality due to risk of bias and imprecision.
ABSTRACTUltrasound is the most widely used medical imaging modality worldwide. It is abundant, extremely safe, portable, and inexpensive. In this review, we consider some of the current development ...trends for ultrasound imaging, which build upon its current strength and the popularity it experiences among medical imaging professional users.Ultrasound has rapidly expanded beyond traditional radiology departments and cardiology practices. Computing power and data processing capabilities of commonly available electronics put ultrasound systems in a lab coat pocket or on a userʼs mobile phone. Taking advantage of new contributions and discoveries in ultrasound physics, signal processing algorithms, and electronics, the performance of ultrasound systems and transducers have progressed in terms of them becoming smaller, with higher imaging performance, and having lower cost. Ultrasound operates in real time, now at ultrafast speeds; kilohertz frame rates are already achieved by many systems.Ultrasound has progressed beyond anatomical imaging and monitoring blood flow in large vessels. With clinical approval of ultrasound contrast agents (gas-filled microbubbles) that are administered in the bloodstream, tissue perfusion studies are now routine. Through the use of modern ultrasound pulse sequences, individual microbubbles, with subpicogram mass, can be detected and observed in real time, many centimeters deep in the body. Ultrasound imaging has broken the wavelength barrier; by tracking positions of microbubbles within the vasculature, superresolution imaging has been made possible. Ultrasound can now trace the smallest vessels and capillaries, and obtain blood velocity data in those vessels.Molecular ultrasound imaging has now moved closer to clinic; the use of microbubbles with a specific affinity to endothelial biomarkers allows selective accumulation and retention of ultrasound contrast in the areas of ischemic injury, inflammation, or neoangiogenesis. This will aid in noninvasive molecular imaging and may provide additional help with real-time guidance of biopsy, surgery, and ablation procedures.The ultrasound field can be tightly focused inside the body, many centimeters deep, with millimeter precision, and ablate lesions by energy deposition, with thermal or mechanical bioeffects. Some of such treatments are already in clinical use, with more indications progressing through the clinical trial stage. In conjunction with intravascular microbubbles, focused ultrasound can be used for tissue-specific drug delivery; localized triggered release of sequestered drugs from particles in the bloodstream may take time to get to clinic. A combination of intravascular microbubbles with circulating drug and low-power ultrasound allows transient opening of vascular endothelial barriers, including blood-brain barrier; this approach has reached clinical trial stage. Therefore, the drugs that normally would not be getting to the target tissue in the brain will now have an opportunity to produce therapeutic efficacy.Overall, medical ultrasound is developing at a brisk rate, even in an environment where other imaging modalities are also advancing rapidly and may be considered more lucrative. With all the current advances that we discuss, and many more to come, ultrasound may help solve many problems that modern medicine is facing.
In certain medical applications, transmitting an ultrasound beam through the skin to manipulate a solid object within the human body would be beneficial. Such applications include, for example, ...controlling an ingestible camera or expelling a kidney stone. In this paper, ultrasound beams of specific shapes were designed by numerical modeling and produced using a phased array. These beams were shown to levitate and electronically steer solid objects (3-mm-diameter glass spheres), along preprogrammed paths, in a water bath, and in the urinary bladders of live pigs. Deviation from the intended path was on average <10%. No injury was found on the bladder wall or intervening tissue.
Applications of ultrasound in medicine for therapeutic purposes have been accepted and beneficial uses of ultrasonic biological effects for many years. Low-power ultrasound of about 1 MHz has been ...widely applied since the 1950s for physical therapy in conditions such as tendinitis and bursitis. In the 1980s, high-pressure-amplitude shock waves came into use for mechanically resolving kidney stones, and "lithotripsy" rapidly replaced surgery as the most frequent treatment choice. The use of ultrasonic energy for therapy continues to expand, and approved applications now include uterine fibroid ablation, cataract removal (phacoemulsification), surgical tissue cutting and hemostasis, transdermal drug delivery, and bone fracture healing, among others. Undesirable bioeffects can occur, including burns from thermal-based therapies and severe hemorrhage from mechanical-based therapies (eg, lithotripsy). In all of these therapeutic applications of ultrasound bioeffects, standardization, ultrasound dosimetry, benefits assurance, and side-effect risk minimization must be carefully considered to ensure an optimal benefit to risk ratio for the patient. Therapeutic ultrasound typically has well-defined benefits and risks and therefore presents a manageable safety problem to the clinician. However, safety information can be scattered, confusing, or subject to commercial conflicts of interest. Of paramount importance for managing this problem is the communication of practical safety information by authoritative groups, such as the American Institute of Ultrasound in Medicine, to the medical ultrasound community. In this overview, the Bioeffects Committee of the American Institute of Ultrasound in Medicine outlines the wide range of therapeutic ultrasound methods, which are in clinical use or under study, and provides general guidance for ensuring therapeutic ultrasound safety.
Low-frequency (LF) ultrasound (20–100kHz) has a diverse set of industrial and medical applications. In fact, high power industrial applications of ultrasound mainly occupy this frequency range. This ...range is also used for various therapeutic medical applications including sonophoresis (ultrasonic transdermal drug delivery), dentistry, eye surgery, body contouring, the breaking of kidney stones and eliminating blood clots. While emerging LF applications such as ultrasonic drug delivery continue to be developed and undergo translation for human use, significant gaps exist in the coverage of safety standards for this frequency range. Accordingly, the need to understand the biological effects of LF ultrasound is becoming more important.
This paper presents a broad overview of bio-effects and safety of LF ultrasound as an aid to minimize and control the risk of these effects. Its particular focus is at low intensities where bio-effects are initially observed. To generate a clear perspective of hazards in LF exposure, the mechanisms of bio-effects and the main differences in action at low and high frequencies are investigated and a survey of harmful effects of LF ultrasound at low intensities is presented.
Mechanical and thermal indices are widely used in high frequency diagnostic applications as a means of indicating safety of ultrasonic exposure. The direct application of these indices at low frequencies needs careful investigation. In this work, using numerical simulations based on the mathematical and physical rationale behind the indices at high frequencies, it is observed that while thermal index (TI) can be used directly in the LF range, mechanical index (MI) seems to become less reliable at lower frequencies. Accordingly, an improved formulation for the MI is proposed for frequencies below 500kHz.