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Therapeutic Ultrasound Spring 2008 Diagnostic Radiology • X-Ray Images – High resolution: < 0.1 mm – Most used in the world Diagnostic Radiology • Fluoroscope Images – Continuously capturing images – Monitoring of surgery Diagnostic Radiology • CT Images – 2D/3D – High resolution 1mm MRI • MRI (Magnetic Resonance Imaging) – – – – – – . Proton Magnetization 3D image Excellent in Soft Tissue Contrast Safer than CT Resolution 1 mm range fMRI: functional, physiological imaging Medical Ultrasound • Medical Ultrasound Imaging – OBGYN – Cardiac Vascular Imaging • Well known Therapeutic Ultrasound – Liposuction – Lithotripsy . Ultrasound Imaging • Safest of all – OBGYN • Low resolution: 5 mm~1mm • fast imaging: for heart imaging – Cardiovascular imaging • Doppler imaging: blood perfusion . Medical Ultrasound • Unknown therapeutic ultrasound – Ultrasound surgery: HIFU – Targeted drug delivery – Trasndermal drug delivery – Gene delivery – Hypo-plastic Left Heart Syndrome – …. Lithotripsy • A lithotriptor is a medical device used in the non-invasive treatment of kidney stones (urinary calculosis) and biliary calculi (stones in the gallbladder or in the liver). • The scientific name of this procedure is Extracorporeal Shock Wave Lithotripsy (ESWL). • Lithotripsy was developed in the early 1980s in Germany by Dornier Medizintechnik. Shock Waves in Atmosphere: Supersonic Aircraft in Nature: Thunder and Lightning in Medicine: Treatment of Kidney Stones Shock Waves Sound p Shock Wave p 100.000.000 Pa (1.000 Bar) 2,2 msec 10 Pa (0.0001 Bar) t t < 2 sec E.g. big church organ playing concert pitch in 5 m distance E.g. Lithotripter shock wave focus Lithotripsy Characteristics of shock waves (in medical applications) Pressure up to 100 MPa (= 1.000 bar) High peak pressure Steep rise time Short pulse time ≈10ns Low tensile wave components ≈300 ns Velocity in water = 1500 m/sec Time ≈ 10 MPa Lithotriptor Electromagnetic Shock Wave + High Energy Density in Treatment Zone Low Energy Density at Skin Level (Anaesthesia-free treatment) Focus Size Shock Wave Applications Urinary Stones Biliary Stones Shock Wave Lithotripsy Tendinopathy Pseudarthrosis Shock Wave Therapy Shock Wave Applications Kidney stone + Shock wave source parameter -6dB Focus size approx. 100 mm 150 mm approx. 5 mm 144 mm Pressure: 3 – 75 MPa Energy Flux Density: 0.005 – 0.65 mJ/mm2 Established Orthopaedic Therapies with Shock Waves - Chronic Pain associated with Tendon Disorders - Pseudarthrosis (non-union) of bones + Orthopaedic Therapy with Shock Waves (calicifying tendinitis of the shoulder) right shoulder left shoulder Pre-shock wave application Enhanced blood flow and perfusion related to shock wave application post-shock wave application Indication for possible application in Cardiology Shock Wave Applications Cardiac Shock Wave Therapy Shock Wave Treatment of Angina Pectoris Angina Pectoris * European Heart Journal (1997) 18 394-413 Angina Pectoris Definition • Angina Pectoris occurs when there is an imbalance between myocardial perfusion and the demand of the myocardium • The pathological substrate of this is almost invariably narrowing of the coronary arteries (coronary atherosclerosis) • It is usually considered that the coronary artery must be narrowed by at least 50 – 70% in luminal diameter before coronary artery blood flow is inadequate to meet the metabolic demands of the heart with exercise of stress Epidemiology • It is estimated that in countries with relatively high coronary heart disease rates, the total prevalent number of patients with angina pectoris may be as high as 30.000 to 40.000 per 1 million total population* * European Heart Journal (1997) 18 394-413 Angina Pectoris Classification of Angina Pectoris (CCS*) • Class I Ordinary physical exercise does not cause angina pectoris • Class II Slight limitation of ordinary activities • Class III Marked limitation of ordinary activities • Class IV Inability to carry on any physical activity without discomfort Aims of Treatment • To improve prognosis by preventing myocardial infarction and death • To minimise or abolish symptoms * Canadian Cardiovascular Society Angina Pectoris Present Treatment Options • Pharmacological treatment of patients with stable angina pectoris • Percutaneous transluminal coronary angioplasty (PTCA) and implantation of stents • Coronary artery bypass grafting (CABG) • Other revascularisation techniques Data on Recurrent Angina • 24% of patients had recurrence of angina pectoris in the first year after coronary artery bypass surgery, 40 % had recurrence after 6 years¹ • After 2 years 31% of patients in the angioplasty group had angina pectoris, compared with 22% in the surgical group² • Restenosis occurs in 35 – 40% of cases with angiographic control ¹ Coronary Artery Surgery Study (CASS) ² Coronary angioplasty versus coronary artery bypass surgery RITA trail, Lancet 1993; 341: 573-90 Angina Pectoris Angina Pectoris Present Coronary Artery Disease Treatment Options Narrowed coronary arteries ▼ Ischemia ▼ Angina Pectoris Atherosclerosis Pharmacological Treatment Angioplasty/Stenting Coronary Artery Bypass Surgery ▼ Multiple interventions Blocked coronary arteries ▼ Necrosis ▼ Myocardial Infarction Lyses Emergency Angioplasty/Stenting & Coronary Artery Bypass Surgery ▼ Multiple interventions Refractory Angina Pectoris: unresponsive to both maximal drug treatment and revascularisation techniques and/or diffuse and distal coronary artery disease New alternative treatments Angina Pectoris New alternative treatment options with various degrees of invasiveness Cardiac Shock Wave Therapy • Pharmacological Treatment • Neurostimulation (TENS & SCS) • Enhanced External Counter Pulsation (EECP) • Laser Revascularisation (PTMR & TMLR) • Therapeutic Angiogenesis Coronary Arteriogram Pre SW (4wks) Post SW (8wks) Control Number of visible Coronary arteries 15 SW Control 10 SW 5 0 Pre treatment Post treatment Shimokawa et al. (Circulation Vol. 110, No. 19, Nov. 9. 2004) Cardiac Shock Wave Therapy (Inclusion Criteria) Refractory stable angina pectoris • Guideline medication • Canadian Cardiovascular Society (CCS) classification III & IV CCS classification I & II for patients refusing or not tolerating other therapies • ≥ 18 years, both gender Liposuction • Modern liposuction first burst on the scene in a presentation by the French surgeon, Dr Yves-Gerard Illouz, in 1982. • Dr. Michele Zocchi invented a technique whereby a sound wave generator is attached to a sterile hand piece with a titanium rod which vibrates at a very high but slightly audible pitch. (UAL) • External ultrasound-assisted liposuction (XUAL or EUAL) – XUAL is a type of UAL where the ultrasonic energy is applied from outside the body, through the skin, making the specialized cannula of the UAL procedure unnecessary. • Ultrashape – No suction, just external ultrasound treatment – 500cc / treatment Types of Liposuction ○ Dry liposuction No injections of local anesthesia This technique was abandoned because of the excessive blood loss Blood composed approximately thirty percent (30%) of the tissue that was removed. ○ Wet Liposuction : Wet Technique also required general anesthesia. the injection of approximately 100 milliliters of local anesthesia containing epinephrine. Blood composed approximately 15% to 20% of the tissue removed by liposuction using the wet technique. Types of Liposuction ○ Tumescent Liposuction The word "tumescent" means swollen and firm injecting a large volume of very dilute lidocaine (local anesthetic) and epinephrine (capillary constrictor) into subcutaneous fat the targeted tissue becomes swollen and firm, or tumescent liposuction totally by local anesthesia. ○ UAL liposuction : the use of a large volume of tumescent fluid Internal UAL is the term used to describe the technique where a long metal probe is inserted into fat through a large incision. External UAL requires the use of tumescent fluid and uses a metal paddle applied to the skin and directs ultrasonic energy into subcutaneous fat. Types of Liposuction ○ Powered Liposuction : PAL devices use power supplied by an electric motor or compressed air a rapid in-and-out movement or a spinning rotation of an attached liposuction cannula ○ LASER Liposuction Using Laser instead of Ultrasound * Ultrashape (no suction) ○ UltraShape technology uses focused ultrasound waves which are directed at a specific target point on the body where they selectively break down unwanted fat cells without affecting surrounding structures. UAL Ultrashape Ultrasound Surgery Ultrasound Surgery Ultrasound Surgery • Characteristics of ultrasound surgery Radiotherapy • Particle wave • Deliver high energy in the intervening tissue • Adverse effect in the intervening tissue • In order to avoid collateral damage focus size becomes order of 10x10x100 cm3 range ultrasound surgery • Mechanical Wave • Absorption less than 5% Most energy propagates thru • Non-toxicity in the intervening tissue • Focus size is 1x1x10 mm3 (Selectivity is much better) Ultrasound Surgery • Frequency: around 1MHz – Wavelength: around 1.54 mm • Focus size: 1 x 1 x 10 mm3 Ultrasound Surgery • Target organs – Liver, prostate, kidney, brain, pancreas, uterus… • Problems in ultrasound surgery – Noninvasive Evaluation tool • Ultrasound Imaging • MRI Imaging – Long Surgery Period – Aberration Correction • Rib cage, Skull Physical mechanism of US • What does cause the tissue damage? – Thermal damage • Even though very small amount of energy is absorbed the target area, if the focus is tight enough and the delivered energy is large enough, there will be heat accumulation. • The accumulated heat can kill cells – Caviational damage • Mechanical rapid collapse of bubble(micro size) inside liquid(body) have highly localized (um range) high concentrated energy effect. Mechanically rupture and high temperature can be induced Thermal Dose • Dose – Concept from radiation dose – Radiation dose • Total absorbed energy from radiation • Factor of attuenaution • Thermal dose – Acoustic energy absorbed thermally – Hyperthermia • Sensitization of tissue to enhance other treatment effect • Less than 43°C – Ultrasound surgery/ tissue ablation • Treatment method • Usually more than 43°C Thermal Dose • Thermal dose tT D ( x, y , z ) R T ( x , y , z ;t ) Tref dt 0 where R e H CT0 ( T0 1) – Tref : reference temperature 43°C – R : 4 when T(t) ≥ 43°C 2 when T(t) ≤ 43°C – Example • • • • At At At At 43°C 44°C 45°C 55°C 50-250 miniutes (usually assumed 240) 120 minute 60 minute 3.5 sec Thermal Dose • Use of thermal dose – Temperature rise estimation • Tissue damage • Surgery planning – Temperature monitoring • Tissue damage estimation • Immediate feedback information • Ultrasound guided Ultrasound surgery – Thermal expansion • MR guided Ultrasound surgery – Proton chemical shift Thermal Dose • Temperature estimation procedure – – – – Acoustic field calculation Acoustic intensity calculation Deposited power calculation Bioheat transfer function calculation • 3D + temporal -> 4D partial differential equation – Thermal dose calculation – Usually the optimization requires repetition of above procedure Ultrasound Surgery Equipment • Extracorporeal type Ultrasound Surgery Equipment • Transrectal type Ultrasound Surgery Ultrasound Surgery Positioning System Imaging Transducer Therapy Transducer Canine Water Bolus Kidney Ultrasound Surgery Ultrasound Surgery Ultrasound Imaging Guidance Ultrasound Surgery Ultrasound Lesion Detection • Step 5 Applying to 2nd set of data in 2D Imaging Modalities for US • MR guided Ultrasound surgery Ultrasound guided Ultrasound surgery • Characteristics – easy to build • Shielding • System cross talk – Fast imaging • almost real time – cheap – low resolution • 10 times worse than MRI • speckles – difficult in temperature measurement Ultrasound guided Ultrasound surgery • Improvement – Tissue characterization : Evaluation tool for various soft tissues characteristics • • • • • Elasticity Temperature Attenuation coefficient Reflectivity Blood perfusion rate MR guided Ultrasound surgery • Characteristics – High Resolution – High sensitivity to temperature • Large calculation time – Difficulty to build • System cross talk • Static Magnetic field – Slow imaging • Reconstruction period – Body motion problem MR guided Ultrasound surgery • Improvement – Temperature measurement • Calculation period – Body motion control – Fast reconstruction – Cost Ultrasound Induced Embolization: droplet vaporization • Droplet: micro-size bubble seed – Becoming macro-size bubble by high frequency ultrasound Canine Brain: Occipital lobe Hypo-plastic Left Heart Syndrome • Shunt: Perforation on Septum • Erosion induced by Focused Ultrasound – Histotripsy – Cavitation, micro-streaming Porcine Atrial Wall Targeted Drug Delivery Targeted drug delivery • Radiation Force Targeted drug delivery • Microstreaming Targeted Drug Delivery • Asymmetric Cavitation Transdermal Drug Delivery • Stratum Corneum – Major resistance of transdermal transport • Some drugs has high permeability – Developed into a patches • Ultrasound transdermal protein delivery – FDA approval in 1995 Bone Growth • Low Intensity Pulse Ultrasound – Bone tissue: Piezo characteristic • Equivalent with electromagnetic pulse – Mechanical Shear stress effect on osteoblast • Ultrasound field induced Micro-streaming Urinary Reflux • Creation of Bubbles in Bladder – Focused Ultrasound Rabbit bladder