|By Tré LaRosa
There are two major overarching principles that guide the study of human biology. First, there is anatomy, or the structure of components – organs, tissues, bones, so on and so forth — of the body; then, there is physiology, or how those parts of the body function. In most if not all areas of the body, such as a joint, it’s not really possible to only study that one component, or at least studying only that one component won’t provide as much insight as considering the joint in the context of its environment. Nor is it really that productive to only consider the anatomy of a body part or system since only studying its structure doesn’t tell us much at all, it’s much more illuminating to also seek to understand its function. Anatomy and physiology aren’t alternative explanations for an underlying truth but are two sides of the same coin.
Imaging techniques help researchers and clinicians to gain a better understanding of anatomy and physiology. Many different technologies exist that provide clinicians images into the many different components of the human body, and they serve different purposes for different patients. There are many, including MRIs, CT, PET and SPECT scans, x-rays, ultrasounds, and EEGs.
Types of Imaging Technologies
Magnetic Resonance Imaging (MRI)
Magnetic Resonance Imaging (MRI) is an imaging technique used to produce detailed three-dimensional images of parts of the body. MRIs are useful for a variety of reasons, including disease diagnosis and monitoring, most notably for soft tissue. These are particularly important and valuable in neurological conditions since MRIs can distinguish between white and gray matter in the brain. For this reason, and due to its reduced risk compared to x-rays and computer tomography (CT) scans, MRIs are the preferred imaging technique for monitoring neurological conditions, though MRIs are more expensive than the alternatives. To produce high-fidelity images of the soft tissue, MRIs employ a cool technique using a large magnet. The description below is from the National Institute of Biomedical Imaging and Bioengineering (NIBIB):
MRIs employ powerful magnets which produce a strong magnetic field that forces protons in the body to align with that field. When a radiofrequency current is then pulsed through the patient, the protons are stimulated, and spin out of equilibrium, straining against the pull of the magnetic field. When the radiofrequency field is turned off, the MRI sensors are able to detect the energy released as the protons realign with the magnetic field. The time it takes for the protons to realign with the magnetic field, as well as the amount of energy released, changes depending on the environment and the chemical nature of the molecules. Physicians are able to tell the difference between various types of tissues based on these magnetic properties.
There exists a subtype of MRI called functional MRI (fMRI) which evaluates blood flow changes in the brain while the patient does different tasks. The intent here is to understand how different parts of the brain are associated with different brain activity, such as thinking about somebody we love (or don’t!), or engaging in certain tasks that require intense focus. fMRI offers an opportunity to understand how different individuals’ brains process the world, including in neurological conditions where there can be cognitive or other associated decline.
X-rays, the oldest medical imaging technique, are used to quickly gain a better understanding of what’s happening in the bones and tissues within the body. X-rays, a form of electromagnetic radiation, are higher energy than other types of light like ultraviolet and visible light, which allows them to pass through most matter. Since different parts of the body have different degrees of radiological density, the amount of x-rays that can pass through varies; this varying amount of x-ray absorption within the body allows the detector to create an “image” of what’s happening within the body. The image, then, depicts the body in various shades of black, white, and grey based on the absorbed x-rays in the imaged tissues or bones. Bones more readily absorb x-rays than other parts of the body, so images of bones produce higher clarity. This is why bones are frequently used to examine breaks and fractures; since bones more readily absorb x-rays, if there is a fracture, more x-rays will pass through where the break or fracture is, allowing the clinician to diagnose the injury.
X-rays do carry risk, though: There is a small increase in the risk a person who is exposed to x-rays will develop cancer later in life, among other small risks. Most of the time, the benefits strongly outweigh the risks.
Due to x-rays’ reliance on the body part of interest’s ability to absorb x-rays, x-rays are not usually used in neurological conditions. This is due in part to the soft tissue nature of the brain; the structure of the brain, and the underlying pathology seen in most neurological conditions, are too granular, subtle, and do not allow for high clarity using x-rays. Recently, however, researchers have developed a modified x-ray technique that allows for 3-dimensional depictions of Alzheimer’s pathology. This technique is still quite novel and early, so it needs further research and investigation before it will be commonplace or used in clinical trials, but promising research is still promising, especially in the field of medical imaging! Researchers continue to innovate to allow for better imaging and understanding of the architecture of the brain and the underlying pathology of neurological conditions. This technique relies on computed tomography, which is a subset of x-ray, and is discussed in further detail below.
Computed Tomography (CT)
Computed tomography (CT) scans utilize x-rays in a different way than conventional x-ray scans in combination with computers to produce clearer, even 3-dimensional, images of the body. Conventional x-rays are fixed, whereas CT scanners rotate to produce a series of images that are then digitized and stacked to produce cross-sections of the body part of interest. These carry the same risk as conventional x-rays but they produce higher-fidelity images that have added value for more complex circumstances. When the cross-sections are stacked, they can be combined to produce a 3D image which allows clinicians and researchers to get a much better — and more realistic — understanding of the body part of interest. These can be used to detect more difficult or deeper bone injuries and abnormalities, bone tumors, even clots in the brain and lungs.
CT scans, then, carry more research and clinical value for neurological conditions. One such study, funded by the National Institute of Biomedical Imaging and Bioengineering, investigated how CT scans could be used as a “one-stop shop” for acute ischemic stroke treatment. They hoped to use one imaging technique — CT, which is common and relatively accessible — to diagnose, triage, and treat patients who had a stroke. With stroke, it is critical that patients receive adequate and immediate care, so reducing all burdens of access, including time, is of utmost important. CT scans offer promise for that reason. Interestingly, though, they might offer other promise in the treatment of neurological conditions.
In one case study (and it should be emphasized that case studies are simply that: single case studies that are not intended to carry the same validation as a clinical trial) from 2016, a patient in hospice with advanced Alzheimer’s dementia received five CT scans over the course of three months. This patient showed remarkable improvement — to the extent where they were actually discharged from hospice care — that all of their family and rotating caregivers noted the significant and relatively quick improvement. The authors of the case study proposed the following mechanism for the improvement: “The mechanism appears to be radiation-induced upregulation of the patient’s adaptive protection systems against AD, which partially restored cognition, memory, speech, movement, and appetite.” Radiation, while it can carry adverse effects, appears to, in low doses, might offer some neuroprotection. This idea needs to be further investigated before any sweeping conclusions can be made, but it’s certainly compelling.
Single Photon Emission Computed Tomography (SPECT) Positron Emission Tomography (PET)
Single photon emission computed tomography (SPECT) and positron emission tomography (PET) scans are similar in design but utilize a different type of electromagnetic light than conventional x-rays and CT scans: gamma rays. SPECT and PET scans also require the use of a radioactive tracer, known as a “radiotracer,” which is a safe, radioactive, FDA-approved compound injected into, or inhaled or ingested by the patient. Both SPECT and PET scans use radiotracers, but the main difference between SPECT and PET scans comes down to two things: the types of radiotracers used, since there are different types of radiotracers for different purposes, and; what they measure, where SPECT scans measure gamma rays directly while PET scans measure “positrons,” which are particles that have nearly the same mass but opposite charge of electrons. NIBIB provides a helpful explanation for how PET scans produce images:
[Positrons] react with electrons in the body and when these two particles combine they annihilate each other. This annihilation produces a small amount of energy in the form of two photons that shoot off in opposite directions. The detectors in the PET scanner measure these photons and use this information to create images of internal organs.
Unlike most of the other imaging techniques listed in this blog, where innovation is mostly related to how the images are taken and processed, PET scans offer another opportunity for innovation: the radiotracers. PET scans are mostly used to diagnose and monitor cancer progress but both PET and SPECT scans have recently become more promising for the diagnosis and maintenance of dementias and Parkinsonian disorders. In Parkinson’s, through the use of what’s called a “DAT SPECT” or “DaTscan,” researchers have found a radiotracer that binds to dopamine transporter molecules. Since Parkinson’s is a condition with lowered dopamine levels in the patients’ brains, DaTscans produce images that show smaller concentrations of dopamine in the brains of patients with suspected Parkinson’s. As for Alzheimer’s, there is an imaging modality called “amyloid PET scan,” where researchers use one of three radiotracers that bind to beta amyloid plaques, one of the hallmarks of AD. Through the use of novel radiotracers, SPECT and PET scans offer a lot of promise for the treatment of neurological conditions, including the aforementioned techniques for AD and Parkinson’s, as well as epilepsy.
While x-rays use x-rays, PET and SPECT scans use gamma ray, ultrasound imaging uses a third type of electromagnetic light: ultrasound waves. Ultrasound also fits into another unique category, similar to what we saw as a possible use case for CT scans: Ultrasounds are used for both diagnostic and therapeutic reasons.
Ultrasounds produce images by using high-frequency sound to produce images of tissues within the body. The sound is emitted and then detected by a probe which produces 2-dimensional images based on the time it takes for the echo to return to the detector.
In terms of neurological conditions, ultrasound — as high intensity focused ultrasound (HIFU) — offers quite a bit of promise, including already being approved in countries across the world for the treatment of tremor, neuropathic pain, and other conditions. Mechanistically, HIFU offers promise due to its ability to harmlessly pass through tissues to converge on a single point for tissue ablation, its ability to neuromodulate without damaging and “open” up the blood-brain barrier, thus facilitating drug delivery. Ultimately, at this point, there remains much more to be learned about ultrasound’s therapeutic value in neurological conditions, but contemporary evidence is very promising.
Electroencephalography (EEG) is a common technique used to measure brain activity. While this technique doesn’t produce an “image,” but rather a series of signals that can be used to gain a better understanding into neurological conditions, EEGs are critical tools in the diagnosis, monitoring, and treatment of neurological conditions. EEGs are particularly useful due to their low-cost and accessibility compared to other techniques used to scan and image the brain.
Many different imaging modalities exist for different reasons. No technique or technology is perfect or without risk, but together they provide a much more holistic, valuable insight into the human body’s natural and abnormal anatomy and functions. They are incredibly valuable for neurological conditions. As novel techniques and strategies arise, they are likely to become even more finely tuned in their ability to diagnose, monitor, and treat neurological — and other — conditions.
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