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Thứ Hai, 25 tháng 11, 2024
Thứ Ba, 19 tháng 11, 2024
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
Thứ Năm, 14 tháng 11, 2024
THERAPEUTIC ULTRASOUND 2024
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
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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.
Thứ Sáu, 1 tháng 11, 2024
Thứ Năm, 31 tháng 10, 2024
Thứ Sáu, 18 tháng 10, 2024
Thứ Ba, 24 tháng 9, 2024
H-Scan Ultrasound
New Ultrasound Technologies Improve Diagnosis for Cancer, Liver Disease and Other Pathologies
Posted on 17 Sep 2024
Several diseases, including some cancers, can remain hidden or difficult to detect using traditional medical imaging. However, new technologies developed by researchers may soon enhance ultrasound's effectiveness in diagnosing conditions such as cancer, liver disease, and other pathologies.
The United States Patent and Trademark Office has recently granted four patents for advanced diagnostic ultrasound technology created by researchers at the University of Rochester (Rochester, NY, USA). Using advanced physics, mathematics, and scattering theory, the researchers have developed techniques to extract previously hidden features from ultrasound data, revealing potential issues with organs like the liver, thyroid, or breast. Some of these innovations have already been licensed to startups aiming to bring these advancements into clinical settings to benefit patients.
Two of the patents are associated with the H-scan technique, while the other two focus on reverberant shear wave fields. The H-scan technology enhances traditional black-and-white ultrasound images by adding color to specific features—for example, coding fat deposits in the liver as yellow or indicating cancer in the breast with red. The technologies related to reverberant shear wave fields improve elastography, which measures tissue stiffness. These advancements provide quicker, more cost-effective methods for delivering critical diagnostic information to doctors and radiologists. Since these technologies focus on ultrasound image processing, they can be seamlessly integrated into existing ultrasound equipment without the need for new hardware.
“These are inventions that you can retrofit to existing imaging systems. You can reprogram the scanners to process our way and out comes this new analysis and information,” said Kevin Parker, the William F. May Professor of Engineering at the University’s Hajim School of Engineering & Applied Sciences, who has developed the ultrasound technologies. “We don’t have to recreate a whole new generation of ultrasound scanners.”
Thứ Hai, 23 tháng 9, 2024
FATTY KIDNEY (FKD)
RECOGNIZING FKD CLINICALLY ‐ THE NEED FOR RADIOGRAPHIC IMAGING
NASH and NAFLD were not reported on abdominal imaging until their clinical importance was recognized. Since then, imaging characteristics of NASH and NAFLD have helped to develop the understanding of fatty liver disease and have led to important innovations.
FKD is currently in the same situation that NASH and NAFLD were 20 years ago. Radiologic reports of MRI and CT scans of the abdomen typically do not elaborate on the presence of ectopic renal hilar or sinus fat, presumably being unaware of its clinical significance. It would help the understanding and recognition of FKD as a distinct entity if radiologists can help define the imaging criteria for FKD.
Currently, renal cortical fat deposits are difficult to measure except with Proton MRI. There are issues of the boundary of the renal capsule and perirenal fat and the paucity of intrarenal fat normally. Advances in renal ultrasound, CT, and MRI may be able to overcome these obstacles and allow a radiographic diagnosis and better characterization.
MRI and CT are presently able to delineate only perirenal fat, hilar fat, and RSF. Hilar fat and RSF should perhaps be considered a combined “entity” because a demarcation is not possible. The assessment of renal triglyceride content by Dutch groups is encouraging. 43 , 44
Noninvasive molecular imaging of kidney disease is progressing and, it is hoped, can measure renal triglyceride/fat as well. 45 , 46
In a weight loss study, MRI was able to assess fat loss in RSF but could not detect any change in renal parenchymal fat. 47
Ultrasound elastography of the kidney may be a technique to measure renal fat content. 48 Sonographic evaluation of para‐ and perirenal fat thickness has been used as a predictor of early kidney damage in obese patients. 35 B‐mode renal ultrasound targeting perirenal fat thickness in specific locations is showing promise. 49 “Para and peri‐renal fat ultrasonographic thickness may be … a useful tool for the assessment of visceral fat and early kidney damage in obese adults”. 35
Much might be learned from such imaging and some centers are beginning the radiographic exploration of FKD. 43 , 46
Because visceral obesity affects multiple organs, it is plausible that FKD occurs whenever NAFLD occurs, as suggested by human 50 , 51 and animal studies. 46
If this is confirmed by imaging studies, it may be possible to infer the presence of FKD whenever NASH is identified, thus obviating the need for specific renal imaging. To the extent that imaging can quantify the degree and location of ectopic fat, there may a quantifiable threshold of visceral obesity that initiates the pathological consequences in the kidney as it appears to do in the liver.
Similarly, there may be implications for recognizing that the location and amount of fat accumulation in other organs, such as the epicardium, determines the extent of pathological consequences, both systemically and to the organ itself.
Pig data show a 100% correlation between the presence of NAFLD and fatty kidney by renal biopsies and triglyceride measured by MRI 7‐Tesla. 46 We postulate that this coexistence also is present in humans, mainly because of many parallel associated factors (metabolic syndrome, insulin resistance, dyslipidemia, proinflammatory state, etc.). No specific type of renal disease has been described when NAFLD and CKD are both present as there are no data published on renal biopsies in that setting. No causal link between NAFLD and CKD has been established, but the relationship has been reviewed in detail. 9
It is certainly possible that the time course and nature of progression of NAFLD to NASH differs from that of FKD to CKD, but they both would be expected to reflect the toxicity of ectopic fat deposits.
FKD (ie, all three stated components: ORG, hilar/renal sinus fat, and intrarenal ectopic fat deposits) has been shown to be a major risk factor for CKD initiation and progression for CKD and hypertension in multiple publications. 7 , 10 , 11 , 24
One key feature of renal cortical lipid deposition (triglyceride and lipid droplets) is podocyte toxicity with albuminuria and CKD development. 23










































