Ever since Wilhelm Conrad Röntgen discovered the X-rays in 1895, medical imaging has played an increasingly important role in clinical diagnostics helping clinicians screen, diagnose and monitor various health conditions. Beginning from a humble X-ray system, which still holds a significant position in medical imaging, the industry has seen the launch of Computed Tomography (CT), Mammography, Ultrasound, Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), Bone Mineral Densitometry (BMD) and various other diagnostic modalities that have revolutionized the diagnostic and treatment protocols in the clinical world. Invasive exploratory surgeries which were considered standard a couple of decades ago, have been largely replaced with diagnostic imaging which are non-invasive and provide the physicians and surgeons with anatomical and functional details up to cellular and molecular levels. Imaging not only occupies an important role in screening and diagnostics but also forms the basis for interventional radiology, radiotherapy and image guidance procedures.
CT and X-ray continue to be the diagnostic modalities of choice for a large number of illnesses. Cathlabs and surgical c-arms have cemented their place in the OR and hybrid suites and look indomitable by any other technology in near future. The non-ionizing technologies such as MRI and Ultrasonography have carved out a superior position for themselves in certain applications. Most of these techniques have been around for at least a few decades and can be labelled as “mature” technologies. Despite the enormous progress made by the imaging industry in the recent past, several challenges have been restricting the utilization of these technologies to their maximum potential. Harmful effects of ionizing radiation are a key barrier for large scale utilization of X-ray based technologies. MRI, CT, and PET are expensive tests and as such not suitable for mass screening. The entire healthcare business is moving toward point-of-care testing and the imaging industry ranks low on portability and miniaturization parameters. Interestingly, there are several technologies in various stages of development which could potentially improvise the efficiency, minimize the harmful effects or challenge the gold standard imaging modalities by virtue of being safe, affordable, convenient, and suitable for mass screening.
In this article, we will briefly explore the promising technologies across different platforms impacting the imaging industry and dwell on the benefits for the clinicians and patients.
1) Innovation in existing imaging technologies
a) Phase Contrast Imaging (PCI)
b) Magnetoencephalogram-Magnetic Resonace Imaging (MEG-MRI)
c) Magnetic Resonance – Positron Emission Tomography (MR-PET)
d) Magneto Acoustic Tomography
2) Biomarkers
a) Liquid Biopsy
3) Bioelectric signals
a) Electroretinogram (ERG) and Visually Evoked Potential (VEP)
4) Optical Technologies
a) Optical coherence tomography (OCT)
b) Capsule endoscopy/ Camera pills
5) Radiowave Imaging
a) Microwave Imaging
1. Innovation in existing imaging technologies
1.1. Phase Contrast Imaging (PCI)
Current x-ray modality is based on the principle of attenuation in varying grades by different tissues in the region of interest being imaged. The generation of contrast is solely dependent on the absorption of x-rays. Phase contrast imaging (PCI) is a new x-ray technology which leverages the diffraction property of tissues to introduce phase shift of the x-ray waveforms passing through it. This allows for a larger spectrum of contrast in x-ray imaging. Soft tissues with differing diffraction properties will be seen with different contrasts, thus increasing the utility of x-rays in non-bone imaging. PCI will utilize very low doses of X-ray than conventional x-ray and increase the spatial resolution as well. Visualization of different contrasts of soft tissue with lower radiation promises a wider spectrum of diagnostic and interventional applications for x-ray and CT. The challenges are that the research studies are all based on giant synchrotron sources of x-ray. Key milestone in realizing this technology would be perfecting the x-ray source from a normal focus or microfocus x-ray tube and an equivalent innovation in the detector sensors to capture the phase change contrasts. With the promise of lower X-ray dose and a broad contrast scale, PCI has enormous potential to disrupt conventional x-ray (diagnostic and interventional), mammography and CT imaging markets.
1.2. MEG –MRI
This hybrid technology combines the Magnetoencephalography (MEG) and ultra-low-field MRI techniques. The advantage with this combination is that the ultra-low field MRI will use superconducting quantum interference device (SQUID) sensors available in MEG instead of RF coils for detection. MEG technology detects the ultra-low magnetic field generated by the electricity in the neurons in the brain. Various institutions are exploring the possibility of using this technology for neuroimaging. Achieving MR signal detection with SQUID devices rather than the RF coils will be a key and significant milestone in the development of this imaging technology that will challenge the current standard standalone MRI and CT for neuroimaging.
1.3. MR – PET
The early PET-MRI imaging used to be done serially with both the equipment placed in adjacent rooms and patient shuttled quickly between these two rooms. With this method motion-induced artefact caused a huge concern in the image output. Truly integrated PET-MRI with single gantry system was introduced by Siemens and this system can be utilised to exploit the advantages of PET and MRI systems in the following disease areas
- Neuro Imaging – Alzheimers Amyloid Imaging
- Cardiac Imaging for assessing the morphology and function of cardiac wall, pericardium, valves, coronary arteries, ischaemia, infarction, wall thickness, wall motion, and so on
- Cancer Imaging – Head & Neck cancer, Breast cancer, Gastrointestinal tumors, Lung cancer, Gynecological cancer, Soft tissue and bone tumors
- Musculoskeletal imaging – joints, ligaments, tendon, osteomyelitis evaluation, and so on
- Inflammatory disorders
- Paediatric imaging in view of the lower radiation dose as compared to PET-CT
What is holding back the wider adoption of MR-PET is a clear definition of the clinical indications in which PET-MRI can be used. The usage has been mostly research based and minimally in clinical settings. While the indications are being defined regulatory and reimbursement issues are expected to be ironed out soon. This hybrid technology has the potential to become the gold standard for oncology imaging and neuro-imaging in the future challenging standalone PET, CT and MRI modalities.
1.4. Magneto Acoustic Tomography
It has been observed that the electrical properties of normal cells and cancerous cells are different. This is expected as a result of the differing water content, membrane permeability, extra cellular fluid and the orientation characteristics of the tumour cells. There are also notable electrical differences between ischaemic cells and normal cells. The differing electrical property between normal and cancerous/ischaemic cells is exploited to form this non-invasive technology. Of different methods to measure the electrical activity, coupling electromagnetic induction with ultrasonic detection seems to be more practical and lower in cost. Magnetoacoustic tomography with magnetic induction (MAT-MI) induces eddy current in the conductive sample and generates acoustic vibrations through Lorentz force coupling mechanism. Ultrasound waves are then sensed to reconstruct the electrical conductivity based image. This technology has enormous applications in cancer screening, diagnosis and treatment monitoring and the potential to challenge PET, CT, MRI, SPECT and mammography. The challenges are in improving sensitivity, instrumentation and reconstruction algorithms which are yet to reach acceptable levels to be used in clinical settings.
2. Biomarkers
2.1. Liquid Biopsy
Liquid biopsies are based on measuring the circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in the body fluids of the affected patients. These cells are released into the blood and other liquid tissues from the tumor. The CTCs are further enriched through specialised instruments and then enumerated to diagnose cancer or to monitor the treatment. The USFDA approved the first liquid biopsy test in June 2016 for the treatment planning of Non-small cell lung carcinoma (NSCLC). Subsequently, various products have been launched for diagnosis and treatment monitoring of lung carcinoma, breast cancer, prostrate and colorectal tumours. Liquid biopsy is increasingly being looked upon as a replacement for surgical biopsies since they have inherent advantages as compared to the tissue samples. Liquid biopsies are also increasingly transcending borders and demonstrating results that match with the gold standard imaging modalities such as PET, CT, MRI, SPECT and mammography in cancer diagnosis and assessing treatment response. Continuing research in liquid biopsies will further promote it to be either used in conjunction with the other imaging modalities or emerge as a standalone tool for cancer screening, diagnosis and treatment monitoring.
3. Bioelectric signals
3.1. Electroretinogram (ERG) and Visually Evoked Potentials (VEP)
Alzheimer’s disease (AD) is a progressive and irreversible neurodegenerative disease which eventually results in cognitive dysfunction and impairs the individual from performing basic routine tasks. Currently, no diagnostic modality assures of 100% sensitivity in AD and the diagnosis is confirmed only on brain autopsy after the individual’s death. Currently the brain imaging studies (CT, MRI and PET) and Cerebrospinal Fluid (CSF) protein studies are at the fore front of biomarker studies. However, these diagnostics are expensive, require elaborate infrastructure and pose a hindrance in screening large populations of the order of millions. Interestingly, in the recent past, several studies have looked at the retina as a possible diagnostic biomarker for AD. Since the eye is a natural extension of the brain, studies have explored and convincingly shown that Aβ plaques and neurofibriallry tangles, which are classical AD pathology seen in the brain tissue, are also seen in the retinal tissue either at the same time or earlier than seen in the brain. This finding has excited the scientific and medical community globally as the changes in the eye pathology can be monitored non-invasively and in a low resource setting without incurring high capital expenditures.
Electroretinogram (ERG) and Visual Evoked Potentials (VEP) in AD retina shows changes such as Slower N35, P50 implicit time, reduced P50, N95 amplitudes, reduced P1 amplitudes, Slower P100 implicit time, etc. Advantages of retinal biomarkers are that they are non-invasive, affordable and can be used for mass screening.
PET Imaging for the diagnosis of AD uses radiotracers with affinity for Aβ plaques and tau proteins. But the disadvantage of PET is that it cannot be used for population screening as it is a costly test, involves irradiation of the subject and a lower spatial resolution. CSF protein studies involve drawing samples through lumbar puncture procedure which makes it an unsuitable candidate for mass screening.
Key challenges of ERG or VEG techniques is that it is of low specificity as other illnesses such as glaucoma and aging also display similar findings. Other tests to rule out age related changes and other systemic diseases can increase the specificity of these tests.
4. Optical Technologies
4.1. Optical coherence tomography (OCT)
OCT exploits the properties of near-infrared light to generate cross-sectional images of the anatomy being studied. The resolution in OCT images ranges from 10 µm to 15 µm and is limited by the diffraction of natural light. OCT can also generate 3D volumetric images which can be valuable tool in cancer assessment. The technology will not involve large capital costs to acquire or to operate but the biggest disadvantage is its shallow depth of penetration (maximum 1 mm).
OCT is a commercialised technology and is already the standard of care in ophthalmology imaging. The technology is also being investigated in the following therapy areas for screening, diagnosis and monitoring.
- Cardiovascular: OCT can be utilized for detailed 3D imaging of the microstructure of coronary walls for the diagnosis of coronary lesions and for guiding interventional procedures.
- Gastrointestinal: OCT will be handy diagnostic tool for a large number of GI diseases and disorders such as Barrett’s Oesophagus, colon polyps, metastatic cancer, and so on
- Respiratory: Lung cancer diagnosis, biopsy, airway remodelling in COPD
- Urinary tract: Transition cell carcinoma, urethral tumors and nerve sparing surgery in prostate cancer
- Gynecology: cervical cancer, ovarian cancer, studying the fallopian tube patency for infertility
- Neuro Imaging: Retinal Nerve Fibre Layer thickness which is a biomarker for Alzhiemer’s Disease’
When OCT application development improvises it is largely expected to emerge as an alternate technology for Intravascular Ultrasound (IVUS) in cardiac applications, CT and MRI in several cancer screening and diagnostics, fluoroscopy in Hysterosalpingogram in Fallopian tube patency exploration and PET Imaging in Alzheimer’s Disease.
4.2. Capsule endoscopy/ Camera pills
Capsule endoscopy is a commercially available technology which uses a small, wireless camera built into disposable capsule which can be swallowed and excreted normally. The capsule travels the entire distance of the digestive tract capturing pictures in thousands until the batteries last and aided by a light source in the capsule. The captured images are transmitted to the paired storage device which is worn on the body. The capsule endoscopy when widely adopted will compete with colonoscopy and CT colon techniques. Adding a magnetic control to direct the flow of the capsule within the GI tract will increase the adoption of this technology amongst the surgeons. Current capsule endoscopy systems compress the images captured and hence the image quality is not satisfactory when compared to the conventional endoscopy systems. Battery life of the capsules also has been a major concern with the current technology as a short battery life could potentially not capture all the images in the region of interest. When these technology issues are ironed out, capsule endoscopy will emerge as a significant tool for screening and diagnosis for GI surgeons.
5. Radiowave Imaging
5.1. Microwave Imaging
Microwave Imaging (MI) for breast cancer detection exploits the dielectric contrast between malignant and healthy tissues. Microwave imaging can emerge as an alternate technology to mammography thus preventing painful breast compressions and exposure to harmful radiation. Microwave technology is also low cost alternative to the pricey ones such as MRI in breast imaging. Ultra-wide-band radar and Tomography are the two approaches being investigated for MI. UWB approach is largely dependent on sensors and the bandwidth of signal. Clinical trials have also demonstrated that it is possible to detect tumors of the size of 1 cm with tomography technique. The drawback of this technology is the heavy computational requirement that leads to a long output time. Studies have employed magnetic nanoparticles as contrast agent to improve the accuracy of the breast cancer detection.
Various technologies across different platforms are in different stages of development to realize a non-invasive, easy-to-use and low-cost device that is suitable for screening, diagnosis and treatment monitoring. Innovation in the existing imaging modalities, liquid biopsy and bioelectric signals look promising and closer to market. These technologies have to be closely tracked to understand whether these developments can blur the significance or form excellent complementary tools for the current standard imaging technologies.
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This article was written with contributions from Dr. Suresh Kuppuswamy, Medical Imaging-Principal Analyst from the Frost & Sullivan’s Transformation Health Practice.
