MS for Rhumatoid Arthritis: New Guidance 2024

 

https://www.medscape.com/viewarticle/new-guidance-clarifies-use-musculoskeletal-ultrasound-2024a1000kxe?ecd=wnl_edit_tpal_etid7010373&uac=130009EX&impID=7010373

THERAPEUTIC ULTRASOUND 2024

https://www.aium.org/resources/official-statements/view/statement-on-biological-effects-of-therapeutic-ultrasound

Ultrasound therapeutic bioeffects are induced through two known mechanisms: thermal and mechanical.11 Thermal effects occur as the result of absorption of ultrasound waves within tissue, resulting in heating.12 Mechanical effects, such as fluid streaming and radiation force,13 are initiated by the transfer of energy/momentum from the incident pulse to tissue or nearby biofluids. Indirect mechanical effects can also occur through interaction of the ultrasound pulse with microbubbles such as ultrasound contrast agents.14 Importantly, thermal and mechanical mechanisms can trigger biological responses that result in desired therapeutic endpoints. Different bioeffects will require different amounts of ultrasound, and thermal and mechanical mechanisms can occur simultaneously for some exposure conditions. The bioeffects that are generated in situ depend on multiple factors, including the tissue properties (eg, density, sound speed, attenuation, backscatter, acoustic impedance, thermal conductivity, perfusion, stiffness), specifications of the therapeutic device (eg, geometry, frequency, pulse duration, pulsing rate, acoustic intensity, and pressure amplitude), and the potential presence of exogenous agents (eg, microbubbles) that promote cavitation bioeffects. Acoustic cavitation is the formation and ultrasound-induced oscillation of gaseous bodies.15 There is a spectrum of cavitation behaviors, which are categorized by two primary descriptors: inertial and stable.16 Inertial cavitation is characterized by a sudden and violent bubble collapse that can potentially damage biological structures. In contrast, stable cavitation is a gentler and repeated bubble oscillation that is less likely to injure tissue.

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Histotripsy

Mechanical bioeffects can also be used to ablate tissue. Histotripsy (histo: cells; tripsy: breaking) applies pulses 1 μs to 10 ms in duration with much higher spatial-peak, pulse-average intensities than used in thermal ablation to generate inertial cavitation (> 20 kW/cm2 for histotripsy compared to 0.001 kW/cm2 for thermal ablation).123, 124 Bubbles formed in the focal zone fractionate cells without heating the target.125 There are multiple types of histotripsy, each of which use different mechanisms to generate bubbles.126, 127 Intrinsic-threshold histotripsy applies pulses of 1 cycle with a peak negative pressure that exceeds ~25 MPa.31 Bubbles are generated due to the tension of the ultrasound pulse. Shock-scattering histotripsy uses highly nonlinear pulses 3 to 20 cycles in duration, with peak negative pressures of 15 MPa or greater. A cloud of bubbles is formed due to interactions between the incident pulse, and the shock wave of the pulse that scatters from bubbles formed in the focal zone.128 Boiling histotripsy relies on pulses 1–10 ms in duration that cause rapid shock wave-induced heating.129 The increased temperature lowers the peak negative pressure required to cause bubble nucleation.130 To date (2024), clinical trials are underway or have been completed to test the safety and technical success of histotripsy technology for the treatment of prostate tissue (NCT01896973), liver (NCT04572633), kidney (NCT05820087), pancreatic adenocarcinoma (NCT06282809), and calcified aortic stenosis (NCT03779620). Further, the FDA granted a de novo request for this technology in the treatment of lesions in the liver.

Pre-clinical studies have demonstrated that histotripsy sensitizes pathologies to other therapeutic approaches. Bubble activity decellularizes tissue, but it is not as effective for breaking down stiff extracellular structures.131 This property of histotripsy can be advantageous for targets that encompass major vessels with extensive collagen and fibrin.132 Extracellular structure can be problematic for applications like venous thrombosis, where fibrin will be undertreated and may serve as a nidus for re-thrombosis.133 Combining histotripsy with a fibrinolytic drug has been shown to treat the cellular and extracellular clot components synergistically.134 Histotripsy has been also shown to enhance the delivery of doxorubicin in a murine model of pancreatic cancer.135

Systemic bioeffects have been observed when histotripsy is applied to free-flowing blood or venous thrombosis without sufficient anticoagulation. The mortality rate of swine in these studies was 45–50% compared to 0% when heparin was administered during insonation.136, 137 The precise cause of mortality in these studies is unknown. There were no cases of vascular perforation or pulmonary embolism. Histotripsy causes significant hemolysis,134 which is a pathway for platelet activation and intravascular thrombosis.138 Microclotting was observed in the heart and lung of pigs that expired during treatment,137 consistent with platelet-induced intravascular thrombosis. Spontaneous thrombus formation may be beneficial when targeting certain lesions. Histotripsy has been applied successfully across the capsule of the liver and kidney without extraneous bleeding issues. This was accomplished when therapeutic and supratherapeutic dose of the antithrombotic warfarin were administered.139 The lack of excessive bleeding was attributed in part due to thromboses in vessels that coincided with the treatment zone. The thrombus resolved over time, as evidenced by patent vessels in follow-up contrast-enhanced imaging.140 Note that the antithrombotic warfarin is not an anti-platelet agent.138

ONLINE COURSE

Introduction to Therapeutic Exercise

Presented by:
Richard Jackson

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The therapeutic effects of US are generally divided into: THERMAL & NON‑THERMAL.

Thermal

In thermal mode, US will be most effective in heating the dense collagenous tissues and will require a relatively high intensity, preferably in continuous mode to achieve this effect.

Many papers have concentrated on the thermal effectiveness of ultrasound, and much as it can be used effectively in this way when an appropriate dose is selected (continuous mode >0.5 W cm-2), the focus of this paper will be on the non thermal effects. Both Nussbaum[19] and Ter Haar[3] have provided some useful review material with regards the thermal effects of ultrasound. Comparative studies on the thermal effects of ultrasound have been reported by several authors[26][27][28][29] with some interesting, and potentially useful results. Further work continues in our research centre with a comparison of contact heating and longwave ultrasound[30] and comparison of different US regimes combined with US (Aldridge and Watson – in preparation).

It is too simplistic to assume that with a particular treatment application there will either be thermal or non thermal effects. It is almost inevitable that both will occur, but it is furthermore reasonable to argue that the dominant effect will be influenced by treatment parameters, especially the mode of application i.e. pulsed or continuous. Baker et al.[2] have argued the scientific basis for this issue coherently.

Lehmann[31] suggests that the desirable effects of therapeutic heat can be produced by US. It can be used to selectively raise the temperature of particular tissues due to its mode of action. Among the more effectively heated tissues are periosteum, collagenous tissues (ligament, tendon & fascia) & fibrotic muscle[32]. If the temperature of the damaged tissues is raised to 40‑45°C, then a hyperaemia will result, the effect of which will be therapeutic. In addition, temperatures in this range are also thought to help in initiating the resolution of chronic inflammatory states[33]. Most authorities currently attribute a greater importance to the non‑thermal effects of US as a result of several investigative trials in the last 15 years or so.

Non-Thermal

The non‑thermal effects of US are now attributed primarily to a combination of CAVITATION and ACOUSTIC STREAMING[3][6][2][1]. There appears to be little by way of convincing evidence to support the notion of MICROMASSAGE though it does sound rather appealing.

CAVITATION in its simplest sense relates to the formation of gas filled voids within the tissues & body fluids. There are 2 types of cavitation ‑ STABLE & UNSTABLE which have very different effects. STABLE CAVITATION does seem to occur at therapeutic doses of US. This is the formation & growth of gas bubbles by accumulation of dissolved gas in the medium. They take approximately 1000 cycles to reach their maximum size. The `cavity' acts to enhance the acoustic streaming phenomena (see below) & as such would appear to be beneficial. UNSTABLE (TRANSIENT) CAVITATION is the formation of bubbles at the low pressure part of the US cycle. These bubbles then collapse very quickly releasing a large amount of energy which is detrimental to tissue viability. There is no evidence at present to suggest that this phenomenon occurs at therapeutic levels if a good technique is used. There are applications of US that deliberately employ the unstable cavitation effect (High Intensity Focused Ultrasound or HIFU) but it is beyond the remit of this summary.

ACOUSTIC STREAMING is described as a small scale eddying of fluids near a vibrating structure such as cell membranes & the surface of stable cavitation gas bubble[33]. This phenomenon is known to affect diffusion rates & membrane permeability. Sodium ion permeability is altered resulting in changes in the cell membrane potential. Calcium ion transport is modified which in turn leads to an alteration in the enzyme control mechanisms of various metabolic processes, especially concerning protein synthesis & cellular secretions.

The result of the combined effects of stable cavitation and acoustic streaming is that the cell membrane becomes ‘excited’ (up regulates), thus increasing the activity levels of the whole cell. The US energy acts as a trigger for this process, but it is the increased cellular activity which is in effect responsible for the therapeutic benefits of the modality[5][6][23][34].

MICROMASSAGE is a mechanical effect which appears to have been attributed less importance in recent years. In essence, the sound wave travelling through the medium is claimed to cause molecules to vibrate, possibly enhancing tissue fluid interchange & affecting tissue mobility. There is little, if any hard evidence for this often cited principle.