Beauty Of Ultrasound Over Decades
Due to its non-invasive nature, low cost, broad diagnostic applicability, and easy handling, ultrasound (US) imaging is the second-most used imaging modality in clinical practice after conventional X-ray radiography. Historically, ultrasound first found its most striking applications in cardiology and obstetrics and later found its way into many other branches of medicine — gastrointestinal surgery, oncology, ophthalmology, musculoskeletal imaging, urology, dermatology, emergency medicine, fetal medicine, neonatology, and others.
Historical evolution
The last 40 years saw a rapid and continuous advancement in the field from A-mode to M-mode, B-mode, Doppler imaging, contrast enhanced ultrasound, US elastography, 2D, 3D, and 4D imaging, laparoscopic, intravascular, endoscopic, and intraoperative ultrasound. It is used as an initial screening tool, as well as for fast-look follow-up examinations. Its ability to visualize blood flow, blood velocity, and blood vessels by power and color Doppler further recommends US imaging for vascular diagnosis. Since its inception more than 40 years ago, ultrasound has undergone dramatic changes from a cumbersome B-mode gantry system to high resolution real-time imaging system.
Principle
Ultrasound is defined as any sound frequency above 20,000 Hz. Sound waves in ultrasound devices are produced by vibrations of specialized crystals- piezoelectric crystals- housed in an ultrasound transducer, with the vibration of crystals produced by pulses of electric current. A proportion of the sound reflected back to the transducer is converted to electric current and displayed as an echo on the ultrasound screen. The transducer acts as both sender and receiver of echoes. The echoes are evident on the screen as varying shades of grey. The frequencies used for medical imaging are generally in the range of 1 to 18 MHz. Higher frequencies, have a correspondingly smaller wavelength, and can be used to make sonograms with finer details.
Merits and drawbacks
Ultrasound has several advantages including portability, low cost, real-time imagery, and freedom from radiation with its attendant side-effects. However, it has certain drawbacks too such as its inability to penetrate bone, poor performance when air intervenes between the transducer and the organ of interest, limited depth penetration especially in obese patients, lack of scout image as with CT and MRI, and operator dependence.
Molecular, multimodal, and theranostic ultrasound imaging
One of the most striking developments in the field of ultrasound has been the coming of age of microbubbles (MB) as the contrast agent for ultrasound. US contrast agents in combination with contrast agent-specific US imaging techniques are used for diagnostic imaging of several organs and pathologies. An important precondition for in vivo molecular imaging is the use of contrast agents which can be detected with high sensitivity and specificity. Microbubbles applied for US imaging fulfills these demands. US contrast agents are gas-filled MB with diameters between 1 and 5 µm. MB also possess the capability of going through small blood capillaries in the body but stay strictly intravascular.
In order to increase the circulation time and reduce the risk of side effects that can arise from coalesced gas bubbles, MB are stabilized by a shell usually made of lipids, proteins, polymers, or a mixture of these. US molecular imaging requires the use of target-specific MB that can selectively bind to intravascular targets. This is achieved by attaching specific ligands, mostly antibodies or peptides, to the MB surfaces, multimodal US contrast agents are particularly useful in (whole-body) biodistribution and histological validation studies. In principle, multimodal US contrast agents make use of the entrapment, attachment, or adsorption of other imaging agents (mostly nanoparticles (NP), radiotracers and small molecules, such as fluorescent dyes for optical imaging) in or on the shell of MB. Examples- US-magnetic resonance imaging, photoacoustic-US Imaging, US-optical imaging, US-nuclear imaging, image-guided drug delivery with MB can be performed either by the co-administration of both drugs and MB, or by the injection of drug-loaded MB.
Therapeutic and theranostic ultrasound
Besides for diagnostic purposes, US can also be used for therapeutic and theranostic purposes. Therapeutic US interventions generally refer to the use of the thermal effects of high-intensity focused US (HIFU). Alternatively, non-thermal effects of US have also been used for therapeutic purposes. For example, US-induced MB cavitation has been shown to facilitate thrombolysis. Similarly, therapeutic agents could be released from nanocarriers by non-thermal effects of US. Theranostic refers to the combination of disease diagnosis (in its broadest sense) and therapy. Theranostic agents can provide valuable information of drug delivery, drug release, and drug efficacy. Higher harmonics are generated as the ultrasound beam propagates deeper into the tissues. Novel approaches such as pulse inversion imaging have been developed based upon this.
Native-tissue harmonic imaging has become a major imaging modality due to its greater penetration depth. The development of microbubbles has led to the development of new forms of imaging like harmonic imaging, perfusion imaging, pulse inversion imaging, pulse inversion doppler imaging, phase-wave contrast imaging, amplitude and phase modulation imaging, temporal maximum intensity projection imaging, and the various forms of intermittent imaging. Technical advances in ultrasound are constantly being made. Developments include portable scanners, miniature pocket-size scanners, and high frequency scanners. High-frequency (above 20 MHz) have been developed for eye, skin, and intravascular ultrasound.
Ultrasound in oncology
Ultrasonography is employed for three basic steps in the staging of neoplastic lesions namely, detection of lesions, diagnosis of their nature, and balance of extension (TNM). Conventional ultrasonography provides a lower diagnostic accuracy than CT and MRI as the balance of extension is concerned, but it yields reliable results for the diagnosis of malignancy if completed by ultrasonography guided percutaneous biopsy. Contrast enhanced US (CEUS) has been found to be useful in lesion detection, characterization of lesions, predicting response in anti-angiogenic therapy, response evaluation following interventional image-guided cancer treatment and in optimization of US-guided biopsies, and as targeted microbubbles, in diagnosis and treatment.
Ultrasound in fetal medicine
No other field has been as transformed by ultrasound as the field of obstetric imaging. The non-invasive nature, lack of radiation, wide availability, real-time imaging capability and portability, all contributed to the explosion of this new discipline. The first application of ultrasound to obstetrics was by Ian Macdonald in 1958. 50 years on, it is impossible to conceive of practicing obstetrics and gynecology without one of the many forms of ultrasound available today. Technological developments such as solid state circuitry, real time imaging, color and power Doppler, transvaginal sonography, and 3/4D imaging have been utilized by clinicians to enhance the investigation and management of patients in areas as diverse as assessment of fetal growth and wellbeing, screening for fetal anomalies, prediction of pre-eclampsia and preterm birth, detection of ectopic gestation, evaluation of pelvic masses, screening for ovarian cancer, and fertility management. Ultrasound guided procedures are now essential components of fetal therapy and IVF treatment. The use of ultrasound in the prenatal diagnosis of fetal genetic syndromes is rapidly evolving. Ultrasound as a screening tool for aneuploidy and other anomalies is increasingly being used throughout pregnancy, beginning in the first trimester. Techniques such as fetal intelligent navigation echocardiography (FINE) detect up to 98 percent of congenital heart diseases.
Ultrasound in neonatology
The field of neonatal ultrasound has been another rapidly evolving specialty. Beginning with its use in the 1980s as neurosonography for assessing the neonate’s brain through the open anterior fontanelle, the discipline has progressed with the introduction of Doppler for assessment of circulation in neonates and has now become part of the acute care doctor’s repertoire. Point-of-care neonatal ultrasound now encompasses neonatal cranial, cardiac, and abdominal ultrasound, hip sonography, and emerging uses in chest, bowel, and functional echocardiography.
Future
Ultrafast imaging using plane waves offers the opportunity to gain quantitative flow information from large vessels, using bubble-specific vector Doppler methods at the same time as imaging perfusion. Two-dimensional matrix array transducers offer real-time volumetric imaging. Molecular imaging using targeted antibodies has the potential in identifying the target and assessing the effectiveness of new therapies. In addition, bubbles are used as potentiators of therapy itself as they can penetrate the endothelial barrier. The drug can circulate in the bloodstream or be incorporated into the bubbles themselves. Plasmid DNA can be carried in the bubble shell and can be used to transfect cells in this new form of gene therapy. The barrier of endothelium can be overcome by injecting liquid nanodroplets- allowing them to diffuse into the interstitium- which can be used to enhance therapy.
Conclusion
Ultrasound has come a long way since the early 1950s. It is one of the most important tools in diagnostic medicine today. Although considered a mature technology, technical advances are constantly being made. The coming years are likely to see an unprecedented union of ultrasound imaging with a unique series of injectable constructs that will propel an already versatile imaging modality to the forefront of the interface between diagnosis and therapy.
