is in molecular imaging with potential clinical applications expected in cancer screening to detect malignant tumors at their earliest stage of appearance. molecular ultrasonography (or ultrasound molecular imaging) uses targeted microbubbles originally designed by dr alexander klibanov in 1997; such targeted microbubbles specifically bind or adhere to tumoral microvessels by targeting biomolecular cancer expression (overexpression of certain biomolecules that occurs during neo-angiogenesis or inflammation in malignant tumors). as a result, a few minutes after their injection in blood circulation, the targeted microbubbles accumulate in the malignant tumor; facilitating its localization in a unique ultrasound contrast image. in 2013, the very first exploratory clinical trial in humans for prostate cancer was completed at amsterdam in the netherlands by dr. hessel wijkstra. in molecular ultrasonography, the technique of acoustic radiation force (also used for shear wave elastography) is applied in order to literally push the targeted microbubbles towards microvessels wall; first demonstrated by dr. paul dayton in 1999. this allows maximization of binding to the malignant tumor; the targeted microbubbles being in more direct contact with cancerous biomolecules expressed at the inner surface of tumoral microvessels. at the stage of scientific preclinical research, the technique of acoustic radiation force was implemented as a prototype in clinical ultrasound systems and validated in vivo in 2d and 3d imaging modes. elastography (ultrasound elasticity imaging) main article: elastography ultrasound is also used for elastography, which is a relatively new imaging modality that maps the elastic properties of soft tissue. this modality emerged in the last two decades. elastography is useful in medical diagnoses as it can discern healthy from unhealthy tissue for specific organs/growths. for example, cancerous tumors will often be harder than the surrounding tissue, and diseased livers are stiffer than healthy ones. there are many ultrasound elastography techniques. interventional ultrasonography interventional ultrasonography involves biopsy, emptying fluids, intrauterine blood transfusion (hemolytic disease of the newborn). thyroid cysts: high frequency thyroid ultrasound (hfus) can be used to treat several gland conditions. the recurrent thyroid cyst that was usually treated in the past with surgery, can be treated effectively by a new procedure called percutaneous ethanol injection, or pei. with ultrasound guided placement of a 25 gauge needle within the cyst, and after evacuation of the cyst fluid, about 50% of the cyst volume is injected back into the cavity, under strict operator visualization of the needle tip. the procedure is 80% successful in reducing the cyst to minute size. metastatic thyroid cancer neck lymph nodes: hfus may also be used to treat metastatic thyroid cancer neck lymph nodes that occur in patients who either refuse, or are no longer candidates, for surgery. small amounts of ethanol are injected under ultrasound guided needle placement. a power doppler blood flow study is done prior to injection. the blood flow can be destroyed and the node rendered inactive. power doppler visualized blood flow can be eradicated, and there may be a drop in the cancer blood marker test, thyroglobulin, tg, as the node become non-functional. another interventional use for hfus is to mark a cancer node prior to surgery to help locate the node cluster at the surgery. a minute amount of methylene dye is injected, under careful ultrasound guided placement of the needle on the anterior surface, but not in the node. the dye will be evident to the thyroid surgeon when opening the neck. a similar localization procedure with methylene blue, can be done to locate parathyroid adenomas. ultrasound-guided hip joint injection joint injections can be guided by medical ultrasound, such as in ultrasound-guided hip joint injections. compression ultrasonography compression ultrasonography is when the probe is pressed against the skin. this can bring the target structure closer to the probe, increasing spatial resolution of it. comparison of the shape of the target structure before and after compression can aid in diagnosis. it is used in ultrasonography of deep venous thrombosis, wherein absence of vein compressibility is a strong indicator of thrombosis. compression ultrasonography has both high sensitivity and specificity for detecting proximal deep vein thrombosis in symptomatic patients. results are not reliable when the patient is asymptomatic, for example in high risk postoperative orthopedic patients. a normal appendix without and with compression. absence of compressibility indicates appendicitis. compression is used in this ultrasonograph to get closer to the abdominal aorta, making the superior mesenteric vein and the inferior vena cava look rather flat. panoramic ultrasonography panoramic ultrasonography of a proximal biceps tendon rupture. top image shows the contralateral normal side, and lower image shows a retracted muscle, with a hematoma filling out the proximal space. panoramic ultrasonography is the digital stitching of multiple ultrasound images into a broader one. it can display an entire abnormality and show its relationship to nearby structures on a single image. multiparametric ultrasonography multiparametric ultrasonography (mpuss) combines multiple ultrasound techniques to produce a composite result. for example, one study combined b-mode, colour doppler, real-time elastography, and contrast-enhanced ultrasound, achieving an accuracy similar to that of multiparametric mri. speed-of-sound imaging speed-of-sound (sos) imaging aims to find the spatial distribution of the sos within the tissue. the idea is to find relative delay measurements for different transmission events and solve the limited-angle tomographic reconstruction problem using delay measurements and transmission geometry. compared to shear-wave elastography, sos imaging has better ex-vivo tissue differentiation for benign and malignant tumors. attributes as with all imaging modalities, ultrasonography has positive and negative attributes. strengths muscle, soft tissue, and bone surfaces are imaged very well including the delineation of interfaces between solid and fluid-filled spaces. "live" images can be dynamically selected, permitting diagnosis and documentation often rapidly. live images also permit ultrasound-guided biopsies or injections, which can be cumbersome with other imaging modalities. organ structure can be demonstrated. there are no known long-term side effects when used according to guidelines, and discomfort is minimal. ability to image local variations in the mechanical properties of soft tissue. equipment is widely available and comparatively flexible. small, easily carried scanners are available which permit bedside examinations. transducers have become relatively inexpensive compared to other modes of investigation, such as computed x-ray tomography, dexa or magnetic resonance imaging. spatial resolution is better in high frequency ultrasound transducers than most other imaging modalities. use of an ultrasound research interface can offer a relatively inexpensive, real-time, and flexible method for capturing data required for specific research purposes of tissue characterization and development of new image processing techniques. weaknesses double aorta artifact in sonography due to difference in velocity of sound waves in muscle and fat sonographic devices have trouble penetrating bone. for example, sonography of the adult brain is currently very limited. sonography performs very poorly when there is gas between the transducer and the organ of interest, due to the extreme differences in acoustic impedance. for example, overlying gas in the gastrointestinal tract often makes ultrasound scanning of the pancreas difficult. lung imaging however can be useful in demarcating pleural effusions, detecting heart failure and pneumonia. even in the absence of bone or air, the depth penetration of ultrasound may be limited depending on the frequency of imaging. consequently, there might be difficulties imaging structures deep in the body, especially in obese patients. image quality and accuracy of diagnosis is limited with obese patients and overlying subcutaneous fat attenuates the sound beam. a lower frequency transducer is required with subsequent lower resolution. the method is operator-dependent. skill and experience is needed to acquire good-quality images and make accurate diagnoses. there is no scout image as there is with ct and mri. once an image has been acquired there is no exact way to tell which part of the body was imaged. 80% of sonographers experience repetitive strain injuries (rsi) or so-called work-related musculoskeletal disorders (wmsd) because of bad ergonomic positions. risks and side-effects ultrasonography is generally considered safe imaging, with the world health organizations stating: "diagnostic ultrasound is recognized as a safe, effective, and highly flexible imaging modality capable of providing clinically relevant information about most parts of the body in a rapid and cost-effective fashion". diagnostic ultrasound studies of the fetus are generally considered to be safe during pregnancy. however, this diagnostic procedure should be performed only when there is a valid medical indication, and the lowest possible ultrasonic exposure setting should be used to gain the necessary diagnostic information under the "as low as reasonably practicable" or alarp principle. although there is no evidence that ultrasound could be harmful to the fetus, medical authorities typically strongly discourage the promotion, selling, or leasing of ultrasound equipment for making "keepsake fetal videos". studies on the safety of ultrasound a meta-analysis of several ultrasonography studies published in 2000 found no statistically significant harmful effects from ultrasonography. it was noted that there is a lack of data on long-term substantive outcomes such as neurodevelopment. a study at the yale school of medicine published in 2006 found a small but significant correlation between prolonged and frequent use of ultrasound and abnormal neuronal migration in mice. a study performed in sweden in 2001 has shown that subtle effects of neurological damage linked to ultrasound were implicated by an increased incidence in left-handedness in boys (a marker for brain problems when not hereditary) and speech delays. the above findings, however, were not confirmed in a follow-up study. a later study, however, performed on a larger sample of 8865 children, has established a statistically significant, albeit weak association of ultrasonography exposure and being non-right handed later in life. regulation diagnostic and therapeutic ultrasound equipment is regulated in the us by the food and drug administration, and worldwide by other national regulatory agencies. the fda limits acoustic output using several metrics; generally, other agencies accept the fda-established guidelines. currently, new mexico, oregon, and north dakota are the only us states that regulate diagnostic medical sonographers. certification examinations for sonographers are available in the us from three organizations: the american registry for diagnostic medical sonography, cardiovascular credentialing international and the american registry of radiologic technologists. the primary regulated metrics are mechanical index (mi), a metric associated with the cavitation bio-effect, and thermal index (ti) a metric associated with the tissue heating bio-effect. the fda requires that the machine not exceed established limits, which are reasonably conservative in an effort to maintain diagnostic ultrasound as a safe imaging modality. this requires self-regulation on the part of the manufacturer in terms of machine calibration. ultrasound-based pre-natal care and sex screening technologies were launched in india in the 1980s. with concerns about its misuse for sex-selective abortion, the government of india passed the pre-natal diagnostic techniques act (pndt) in 1994 to distinguish and regulate legal and illegal uses of ultrasound equipment. the law was further amended as the pre-conception and pre-natal diagnostic techniques (regulation and prevention of misuse) (pcpndt) act in 2004 to deter and punish prenatal sex screening and sex selective abortion. it is currently illegal and a punishable crime in india to determine or disclose the sex of a fetus using ultrasound equipment. history after the french physicist pierre curie's discovery of piezoelectricity in 1880, ultrasonic waves could be deliberately generated for industry. in 1940, the american acoustical physicist floyd firestone devised the first ultrasonic echo imaging device, the supersonic reflectoscope, to detect internal flaws in metal castings. in 1941, austrian neurologist karl theo dussik, in collaboration with his brother, friedrich, a physicist, was likely the first person to image the human body ultrasonically, outlining the ventricles of a human brain. ultrasonic energy was first applied to the human body for medical purposes by dr george ludwig at the naval medical research institute, bethesda, maryland, in the late 1940s. english-born physicist john wild (1914–2009) first used ultrasound to assess the thickness of bowel tissue as early as 1949; he has been described as the "father of medical ultrasound". subsequent advances took place concurrently in several countries but was not until 1961 when david robinson and george kossoff's work at the australian department of health resulted in the first commercially practical water bath ultrasonic scanner. in 1963 meyerdirk & wright launched production of the first commercial, hand-held, articulated arm, compound contact b-mode scanner, which made ultrasound generally available for medical use. france léandre pourcelot, a researcher and teacher at insa (institut national des sciences appliquées), lyon, co-published a report in 1965 at the académie des sciences, "effet doppler et mesure du