One of the most exciting recent developments in imaging consists of all-optical ultrasound. Unlike traditional ultrasound, which is achieved using piezoelectric transducers, optical systems perform ultrasonic generation via pulsed light. This is followed by optical reception of ultrasonic reflections from the tissue which is being imaged.

Reducing the need for trade-off
Though ultrasound is one of the most common medical imaging tools, conventional devices tend to be bulky and cannot typically be used at the same time as some other imaging technologies. This is why a hybrid combination of optics and ultrasound, coupled to inexpensive fibre-based probes for intravascular imaging, promises to open up new possibilities for medical imaging. 
In terms of imaging, optical techniques ensure satisfactory contrast levels, while ultrasound provides high resolution. Optical technologies can also be manipulated to generate low frequency ultrasound which yields greater penetration into tissue, or high frequency ultrasound to obtain higher resolution images, albeit at a shallower depth. In practical terms, such a combination also gives flexibility to physicians in how they use imaging technology to diagnose and treat medical problems. For example, to provide intravascular imaging and detection of conditions like plaque, ultrasound can provide details of morphology while the optical imaging highlights its composition.

Broadband imaging
In technical terms, traditional ultrasound image formation covers a narrow frequency band (usually half the central frequency), while signal generation in optical ultrasound is broadband (covering sub-MHz to several hundred MHz frequencies). In addition, the tomographic principles used by optical ultrasound generally entail data collection over wide angles. This improves image quality and resolution, while minimizing image artifacts.
Efforts to develop broadband all-optical ultrasound transducers date to over a decade. One prototype was developed and tested for high-resolution ultrasound imaging in 2007 at the University of Michigan, Ann Arbor. It consisted of a two-dimensional gold nanostructure on a glass substrate, followed by polydimethylsiloxane plus gold layers. The system achieved a signal-to-noise ratio of a pulse-echo signal of over 10dB in the far field of the transducer, where the centre frequency was 40MHz with −6dB bandwidth of 57MHz. In a paper published in the August 2008 issue of ‘IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control’, the developers of the system concluded that preliminary imaging results “strongly suggest that all-optical ultrasound transducers can be used to build high-frequency arrays for real-time high-resolution ultrasound imaging.”
Innovation not enough to offset drawbacks
As mentioned, the major driver of research into hybrid optical alternatives has consisted of limitations in conventional ultrasound systems. Such drawbacks persist in spite of developments in processing speed, a reduction in noise-to-signal ratios and enhancement in the quality and timing of image capture.
Although innovations such as matrix transducers have enabled the emergence of volumetric ultrasound and 3-D/4-D, elastography has offered physicians the ability to view both stiffer and softer areas inside of tissue.
Elastography uses b-mode ultrasound to measure the mechanical characteristics of tissues, which are then overlaid on the ultrasound image. However, its use in clinical practice remains complicated due to a wide range of techniques used by different manufacturers, alongside differences in parameters used to characterize tissues.
Other areas of innovation include micro-ultrasound, which harnesses ultrasound at microscopic levels and provides 3- to 4-fold improvements in resolution compared to conventional ultrasound. One of the first applications of micro-ultrasound is to allow better targeting of biopsies – for example, in the treatment of prostate cancer by urologists.

Ultrasound-modulated optical tomography
In the late 2000s, ultrasound-modulated optical tomography (UOT) showed considerable promise in imaging of biological soft tissues, with promising application in several areas, including cancer detection. UOT detects ultrasonically modulated light to localize and image subjects. The key limitation of UOT, however, is weak modulated signal strength.

Photoacoustic tomography
Considerable attention has also been given to photoacoustic tomography, which converts absorbed light energy into an acoustic signal. The technique provides compositional information on body tissue in real time without requiring any contrast agents. It also allows much higher depth penetration than conventional optical techniques. Photoacoustic tomography has been used for mapping the deposition of lipids within arterial walls.
Photoacoustic tomography begins by sending pulsed light into tissue, typically from a Q-switched Nd:YAG laser. This creates a slight hike in temperature which causes the tissue to expand, creating an acoustic response which is detected by an ultrasound transducer. The data is then used to visualize the tissue.
However, photoacoustic tomography systems have proved difficult to translate into clinical applications due to their high cost, as well as a relatively large footprint which requires a dedicated optical table to house the laser. On a technical level, moreover, a low pulse repetition rate (in the dozens of hertz) prevents photoacoustic tomography from being used in high frame rate imaging, which are required for clinical applications such as cardiac related problems, where the rate of blood flow is high, or in other similarly fast-moving settings.
There are nevertheless several efforts to cope with the challenges facing photoacoustic tomography. The first is enhancing signal-to-noise ratio and the depth of penetration of optical absorbers. Researchers at Purdue University in the US, who are at the forefront of investigations into the technique, believe that new optical manipulation techniques to maximize photon density might provide a way forward. They have recently announced development of a motorized photoacoustic holder, which allows manoeuvring the aim of the device and fine-tuning the depth to where light is focused. This, they believe, could significantly improve light penetration as well as the signal-to-noise ratio.
Other efforts seek to cope with fast-moving and dynamic settings. In Singapore’s Nanyang Technological University, for example, researchers have demonstrated up to 7,000 Hz photoacoustic imaging in B-mode, using a pulsed laser diode as an excitation source and a clinical ultrasound imaging system to capture and display the photoacoustic images.

All-optical ultrasound
All-optical ultrasound, which has recently catalysed maximum interest, involves using pulsed laser light to generate ultrasound. Scanning mirrors control where the waves are transmitted into tissue. After this, a fibre optic sensor receives the reflected waves, recombines them and creates a visualization of the area being imaged.

Bandwidth, acquisition time and electromagnetic interference
Such a modality exhibits wide bandwidth and satisfactorily addresses one of the major shortcomings of previous efforts at clinical application – namely, prolonged acquisition times (ranging from minutes to hours). Unlike conventional ultrasound imagers which use electronic transducer arrays to transmit sound waves into tissue and receive the reflections for reconstruction as images by a computer, all-optical ultrasound imagers are also immune to electromagnetic interference. As a result, an all-optical ultrasound system can be safely used alongside a magnetic resonance imaging (MRI) scanner, allowing physicians to obtain a more comprehensive picture of tissues around an area of interest, such as a tumour or blood vessel. Immunity from electromagnetic interference and MRI compatibility also means that all-optical ultrasound can be used during brain or fetal surgery, or for guiding epidural needles.

Miniaturization
The absence of electronic components gives yet another advantage, too. Components of conventional ultrasound devices are difficult to miniaturize for internal use. This is due to two factors: a drop in sensitivity after a reduction in the area of the active piezoelectric transducer, and the impact on size of the transducer due to the casing of the piezoelectric element and electrical insulation.
Miniaturization is particularly important in minimally invasive measurements such as medical endoscopy or for inspection of the lumen in non-destructive testing. Small-area detectors are also preferred in tomographic applications, given that detector size inversely correlates to spatial resolution.
Due to difficulties in miniaturization, most ultrasound devices use large, handheld probes placed against the skin. Although some high-resolution probes have been developed, they are considered too expensive for routine clinical use.
Unlike the above limitations for conventional ultrasound devices, the miniaturization of optical detectors (e.g. via interferometric resonators) does not impact on active detection area. In other words, there is no loss of sensitivity. Finally, optical components are not only easily miniaturized but also significantly less expensive to manufacture, compared to compacting electronic ultrasound systems.

First video-rate all-optical ultrasound system
The world’s first all-optical ultrasound system capable of video-rate, real-time imaging of biological tissue has been demonstrated by a research team from University College London (UCL) and Queen Mary University of London (QMUL). It was used to capture the dynamics of a pulsating ex-vivo carotid artery within the beating heart of a pig, and revealed key anatomical structures required to safely perform a transseptal crossing, namely left and right atrial walls, the right atrial appendage and the limbus fossae ovalis.
The researchers believe the new technology will allow ultrasound to be integrated into a wide range of minimally invasive devices in different clinical contexts, and provide ultrasound imaging of new and previously-inaccessible regions of the body. Above all, its real-time imaging capabilities allows differentiation between tissues at significant depths, helping to guide surgeons in some of the highest risk moments of procedures. This will reduce the chances of complications occurring in cases such as cardiac ablation.

Designed for clinical advantage
The new system from UCL and QMUL uses light guided by miniature optical fibres, encased within a customized clinical needle, which generate ultrasonic pulses. Reflections of these ultrasonic pulses from tissue are detected by a sensor on a second optical fibre, in order to provide the real-time imaging.
The developers based their design on a nano-composite optical ultrasound generator coupled to a fibre-optic acoustic receiver with extremely high sensitivity. In turn, harnessing eccentric illumination provided an acoustic source with optimal directivity. This was then scanned with a fast galvo mirror which provided video-rate image acquisition (compared to a time-frame of several hours in previous experiments). It also increased image quality in both 2D and 3D, and made it possible to acquire the images in different modes.
The scanning mirrors in the new system are flexible. They allow for seamless toggling between 2D and 3D imaging as well as a dynamically adjustable trade-off between image resolution and penetration depth. Unlike conventional ultrasound systems, these are achieved without requiring a swap of imaging probe. In a minimally invasive interventional setting, in particular, such probe swapping extends procedure times and introduces risks to the patient.
The technology has been designed upfront by the researchers for use in a clinical setting, with sufficient sensitivity to image moving tissue inside the body at centimetre-scale depth and fit into existing workflow. The researchers are currently working on developing a flexible imaging probe for free-hand operation, as well as miniaturized versions for endoscopic applications.

Since its introduction in 1973, X-ray computed tomography (CT) has become a leading modality for diagnostic imaging. The advantages of CT are manifold. Above all, they include rapid scanning and small spatial resolution, which allows for relatively quick and accurate diagnosis of injuries and disease. CT has also been an imaging tool of choice for the staging and treatment follow-up of cancer.

Growth in use, but variations between countries
Overall, CT use has grown rapidly. The total number of scans in the US is estimated to be in the region of 80 million a year. In England, the National Health Service (NHS) reported 4.8 million CT scans in 2016/17, which is 40 percent more than the 3.4 million MRI scans done during that year. CT usage has also been growing rapidly – in England at about 8% annually, compared to just 1.5% for X-rays and 5% for ultrasound.
Nevertheless, there are significant variations between countries in the intensity of CT use. According to data from the Paris-based Organization for Economic Cooperation and Development (OECD), the annual rate of CT scans per 1,000 inhabitants ranges from a high of 225-230 in the US and Japan, to a low of 37 in Finland. The rate is about 80 in Italy, 90 in the Netherlands, 110 in Spain, 140 in Germany and 200 in Belgium and France.
Differences in radiation dosing practice
Though large, such divergences are considered to be less significant than differences in radiation dose to which patients are exposed, for the same condition. In December 2007, a study published in ‘European Radiology Supplement’ had found dosage could have been halved in many cases without impacting on image quality. Another study two years later revealed a 13-fold difference between the lowest and highest radiation doses used for identical CT procedures by four clinical sites in the neighbourhood of San Francisco.
Concerns about such issues have been dramatically highlighted after a major new international study, which attributes differences in dosage to the person doing the scanning rather than to patients or equipment. The study, published in ‘The British Medical Journal’ (BMJ) in January 2019, found that patient characteristics, make and model of scanner, and type of hospital where the CT scan was done had little effect on the amount of radiation used.

Analysis of 2 million CT scans in 151 institutions
The BMJ study was based on a massive effort by a research team led by Dr. Rebecca Smith-Bindman, a professor in the Department of Radiology and Biomedical Imaging at the University of California San Francisco (UCSF). The researchers analysed dose data for over 2 million CT scans of the abdomen, chest and head, at 151 institutions in seven countries.
Their findings are likely to resonate strongly, given the association of radiation with cancer. Although CT scans account for a minority of diagnostic radiologic procedures, they use large amounts of radiation per image. Some estimates suggest that CT contributes nearly half the US population’s radiation dose from all medical examinations. The figure in England is higher, at 68 percent, although plain radiography is used five times more often than CT in the country (22.9 million procedures in 2016/17 versus 4.8 million).

Cancer risks of CT
The association with cancer has been controversial, especially when predictions of the impact of CT scanning have been based on a linear-no-threshold dose-response model. Some have argued that CT radiation doses are too low to produce any health effect.
There is also uncertainty about how to calculate risk accurately. This is because of a host of factors. Firstly, radiologists are not necessarily familiar with CT radiation exposure descriptors (volume CT dose index and dose length product). Secondly, there have been a series of revisions about the relative sensitivity of organs to radiation. Finally, radiation dose in units such as millisieverts (mSv) are used to estimate population risks based on generic models, not individual patient calculated dose. Indeed, the radiation dose in a typical CT scan (1–14 mSv depending on the exam) is similar to the annual dose received from natural sources, such as radon and cosmic radiation – which typically varies from 1 to 10 mSv, depending on where a person lives.

Even small risks justify search for solutions
Nevertheless, the current consensus is that, even if the risk of cancer from CT imaging is small, the economic burden of treatment of the proportionately reduced number may well be significant, given the high prices of cancer treatment.
Neither does anyone question the logic of attacking even a small cancer risk. In December 2009, a report in ‘The Archives of Internal Medicine’ made a detailed assessment of projected cancer risks due to CT scans in the US. The study was conducted by a team from the Radiation Epidemiology Branch of the National Cancer Institute (NCI), and argued that changes in practice might help to avoid the possibility of reaching an attributable risk of 29,000 cancer cases based on CT scans in the year 2007. The authors also observed that the impact would be largest in abdomen, pelvis and chest CT scans in adults aged 35 to 54 years.

Unnecessary scans
One of the most vexatious issues concerns CT scans which are not medically necessary, especially when it concerns repeat imaging of a particular patient – and the ensuing enhancement of cancer risk. According to one estimate, unnecessary scans could account for as much as 30 percent of CTs in the US. In Europe, such a figure is also likely to be high in countries such as Belgium and France where per capita CT scan levels are close to those of the US.
Though the US state of California has passed a law requiring documentation in a patient’s medical record of radiation dose used for every CT scan, compliance has been inconsistent. Perspectives in Europe are problematic too. For example, the European Union collects dose levels in Europe, but there are major differences in definitions and data collection techniques.

Progress in pediatric dosing
Until the NCI study at the end of 2009, the emphasis on reducing CT cancer risks had largely been on pediatric scans. The authors of that paper noted there was evidence of pediatric doses being reduced as a result of social marketing campaigns such as Image Gently. The latter was launched in 2008 by the Alliance for Radiation Safety in Pediatric Imaging.

Lessons from the pediatric dose control campaign
One of the key recommendations of Image Gently was to promote standardization of pediatric dose measurements and display across vendor equipment.
This is precisely what the recent BMJ study proposes to do for all patients. The authors of the study assessed mean effective doses and proportions of high dose examinations (defined as CT scans with doses above the 75th percentile defined during a baseline period) for abdomen, chest, combined chest and abdomen, and head CT. These were classified by patient characteristics (sex, age, and size), type of institution (trauma centre, 24×7 care provision, academic and private hospital), practice volumes, machine manufacturer and model, country etc. The figures were adjusted for patient characteristics, using hierarchical linear and logistic regression.
For example, after taking into account patient factors, a fourfold range in radiation doses still existed in abdominal scans. Similar variations were found for chest and combined chest-and-abdomen scans.

Huge variations in dose
The BMJ study found that variations in radiation dose across institutions and countries were huge. For abdomen CT examinations, the mean effective radiation dose differed by a factor of four, with a 17-fold range in the share of high dose examinations (4 to 69%). Variations in mean effective dose for chest scans and combined chest plus abdomen scans were also close to four times, while the share of high dose exams varied from 1 to 26%, and 2 to 78%, respectively. For head CT, the differences were less spectacular (with the range of mean effective doses less than 1.5 times and the share of high dose exams ranging from 8 to 27%.

Achievable and universal standards
However, when the UCSF group adjusted for technical parameters, that is, in terms of the way CT scanners were used by medical staff, the variations in doses nearly disappeared.
The researchers conclude that it is possible to optimize doses to a “single set of achievable quality standards” and apply this “to all hospitals and imaging facilities.” They also noted that the choice of “appropriate CT protocol parameters might be less complex than widely believed.” The key to protocol optimization lies in updating physician awareness and recalibrating expectations about what constitutes a diagnostic CT scan. The latter will be based on a better alignment of CT protocol parameter choices with diagnostic image quality requirements.
One interesting finding was that institutions with lower average doses shared scanning approaches. These institutions tended to limit the number of protocols, with each relying on the minimum dose required to answer the clinical question. They used multiple CT scanning infrequently, had lower settings for tube current and tube potential, and used higher pitch for most, if not all, imaging indications.

The way ahead
The road to CT dose reduction and standardization will vary by type of institution and country. This is due to differences in the make and model of CT scanners as well as medical cultures, in terms of radiologist preferences and personnel support. There are case studies of protocol overhauls taking a year or more, and needing to be kept up-to-date with new CT software and scanner upgrades. Examinations with higher radiation exposure generally give more acceptable images than those where exposure is lower. The challenge is to optimize a ‘correct’ minimum dose for different patient sizes, ages and conditions. Continuing improvements in scanning technology will undoubtedly also be part of the process of optimizing protocols. On their side, some companies have been experimenting with artificial intelligence algorithms to position patients correctly in a CT scanner. Off-centre CT scans can expose patients to much higher levels of radiation
than necessary.