The Future of Continuing Education in Diagnostic Imaging

Common Pathology & Imaging of the Brain

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Authors: Karen Vieira, PhD, MSM & Deirdre O'Donnell, M.Sc.

Abstract: This article is intended to deliver an overview of brain pathology and how it relates to neuroimaging. Imaging techniques have improved and advanced the development of neurology for the last few decades. Currently, modalities such as positron emission tomography, magnetic resonance imaging and computed tomography are standards in the diagnosis and analysis of neuropathology. This article will outline their roles in this for common events such as traumatic brain injury and ischemic stroke. Additional pathologies will also be described and outlined in terms of imaging. As modern imaging techniques may also influence treatment choices, and responses to treatment, the treatment of these pathologies will also be outlined. This article will also discuss the roles of standard forms of CT and MRI in neuropathology, as well as some of their more up-to-date variations. It is intended to contribute to the ongoing education of radiologic technologists.

 

 

Introduction

 

The brain is an organ for which disease and pathology represent an often significant impact on the quality of life for a patient. However, both the brain and the conditions that affect it are difficult to study without techniques that allow the visualization of its structure and how it relates to normal and abnormal function. The skull, meninges and (in some cases) the blood-brain barrier (BBB) have historically posed challenges to the attempted non-invasive imaging of this organ. These layers of tissue were related to distortion, signal loss and other forms of quantitative bias or error that made it difficult to image the brain accurately. In addition, modalities such as plain radiography were often not sensitive to the different types of tissue within the brain. However, modern forms of imaging can correct for the signals of potential detractors such as cerebrospinal fluid (CSF, found in layers within the meninges). It may also allow for the improved distinction between different regions, structures and even cell types of the brain.

 

Imaging may also negate the need for biopsy and other diagnostic procedures that involve the physical breach of any structures immediately outside the brain. These pose a range of risks and potential side-effects for any patient. The brain is an important component of the central nervous system (CNS). The meninges and BBB are vital factors in its optimal function and protection. Damage to these structures may result in motor defects, sensory anomalies or the onset of chronic pain. Other side-effects of invasive neuropathology testing include the leaking and/or loss of cerebrospinal fluid (CSF). This may result in symptoms such as acute headache. Therefore, recent developments in brain imaging have been an unqualified boon for many doctors and researchers. Brain imaging has greatly improved the understanding of the organ, and of how individual pathologies may affect it. The role of the registered technologist (R.T.) is to provide and maintain the equipment and technology required to deliver brain imaging, manage radiological equipment and treatments administered to patients as required, and to optimize their knowledge of the techniques and diagnostic skills necessary for the optimal visualization of individual pathologies.

 

 

Imaging Modalities/Techniques & Their Applications in Brain Imaging

 

Computerized Tomography

 

Computerized tomography is a computer-aided form of X-ray analysis, typically resulting in axial images of the organ or system under evaluation. The development of this technique in the 1970s was the beginning of a new era in neuroimaging. Previous to this, the field was restricted to adaptations of other general forms of medical imaging, including basic X-ray techniques, and indirect forms of imaging such as encephalography and myelography [1]. In fact, CT was initially restricted to scanning the brain due to technological constraints on whole-body imaging [1]. There are some variations on CT employed in neuroimaging, including:

 

  • Multi-detector/multidetector-row CT: This involves a two-dimensional array of detector elements. This results in increased complexity of image construction, but also allows for the generation of multiple slices. Multi-detector CT also generates images of high resolution, and three-dimensional (3D) capability through the use of isotropic voxels [1]. 4D CT - i.e. functional CT, or 3D scans in conjunction with perfusion, are increasingly feasible applications that may be widely available in the near future [1]. CT with perfusion demonstrated significantly superior prediction of an infarct as a complication of ischemic stroke in a study including 76 patients with this condition in comparison with conventional CT or CT angiography [2].
  • Dual-energy CT (DECT): As the name suggests, these are images based on the recombination of images from two separate yet simultaneous X-ray sources. This allows for the improved differentiation of tissues based on variations in attenuation [1]. This allows for the superior detection of pathologies such as hemorrhage [1]. DECT is often delivered by two tubes firing at two different set values (e.g. one at 80kVp and one at 140kVp) or one tube switching between these in near-real time [1]. Alternatively, DE data may be acquired by measuring the intensities of high- and low-energy photons from a polychromatic source [1]. DECT may also allow for serial scanning of intensities from a single source [1]. These adaptations allow for the differentiation and/or nullification of certain tissues (e.g. bone) based on properties such as their atomic number [1].

 

These adaptations may also enhance scans of specific tissues, e.g. CT angiography (which is employed to detect suspected infarcts or ischemic stroke) [1, 2]. Conventional CT of the brain is often indicated to assess mild to moderate head injuries [3]. This standard procedure may detect large-scale forms of pathology as a result of traumatic brain injury, such as hemorrhages. CT is also often used to assess the possibility of brain infarcts in older, at-risk patients [4]. However, it may miss 'finer' details of trauma, such as diffuse vascular or axonal injury [5]. (Diffuse axonal injury (DAI) is a term for widespread white matter damage as a result of damage to the axons, or the terminals at which one nerve cell interacts with another. DAI is particularly associated with traumatic brain injuries, and may result in severe impairments of brain function [6].) A recent study indicated that pathologies detected on the CT scans of patients with mild traumatic brain injury had poor predictive value in affecting long-term outcome measures (overall function and self-reported symptoms. This study found increased age and female gender were more likely to affect these factors than anomalies detected on CT.) [3]. A study including 136 intensive care unit patients indicated that magnetic resonance imaging (MRI, see below) was more sensitive in detecting pathologies such as ischemic or hemorrhagic lesions in comparison to CT [7]. MRI is also often preferred when assessing signs of neurodegenerative conditions, such as white matter changes and temporal lobe atrophy [4]. A 2009 study assessed the ability of three raters blinded to the diagnosis of 30 patients to detect atrophy on images generated by multidetector CT and others generated by MRI, using a simple visual rating scale. The results indicated that the sensitivity for cortical and medial temporal atrophy of CT was similar to that of MRI [8]. This indicates that CT is effective in the detection of these anomalies when standardized rating systems are used. A retrospective study of the CT scans from 94 patients over 60, originally intended to assess age-specific risks such as infarcts, found that the images showed adequate sensitivity for cortical atrophy, temporal atrophy and white matter changes when evaluated by a neuroradiologist blinded to all other patient information [4]. The ratings for all three anomalies correlated well to the Min-Mental State Exam (a 30-point test typically given to patients with suspected dementia or other similar pathologies that assesses various facets of cognition, orientation in time, language skills and recall [4]) scores given by the patients in conjunction with CT [4].

 

Single Photon Emission Computerized Tomography

 

Single photon emission computerized tomography (SPECT) is another form of CT. SPECT images may be generated using tracer isotopes, as with positron emission tomography (see below) [9]. Typical SPECT tracers include 123I and 99mTc [8]. This technique is useful in determining cerebral blood flow (CBF). CBF is another well-validated and common measure of brain activity. Local or widespread reductions in CBF are indicators of probable brain damage or CNS pathology [10].

 

Magnetic Resonance Imaging

 

Magnetic resonance imaging (MRI) is one of the most common techniques used in the visualization of brain pathology. Water and fat molecules are ubiquitous in the brain. Therefore, techniques that generate images based on the analysis of resonance within these are plainly useful to neurologists. These images are also often generated using contrast material or agents. Contrast agents are administered into the CNS in order to enhance contrast between brain tissue and the background signal (or 'noise') [11]. The appropriate and correct use of contrast material is particularly important, as this 'noise' may invalidate the appearance of any anomalies on an MRI-generated image. Gadolinium compounds are prominent examples of MRI contrast agents [11]. Superparamagnetic iron oxide is an example of an alternative agent[11]. These are mostly used to visualize lymph tissue abnormalities.

 

Contrast agents may increase the visibility of gross pathology (e.g. advanced neurodegeneration) on MR-generated images. They may also enhance imaging at the cellular or even molecular level [11]. Examples of this are the breakdown of the BBB, which is a hallmark of the final stages of many neurological conditions, and the recruitment of leukocytes to damaged neural tissue, which may be seen in conditions such as multiple sclerosis [11]. Imaging on this scale is one of the best tools in visualizing pathology in the absence of relatively large-scale (i.e. anomalies that are more apparent on a whole-brain image) structural defects. Some researchers are working on the development of 'smart' contrast materials that purport superior 'targeting' of this pathology type in comparison with conventional agents [11]. These scientists claim that developments in contrast agent technology will enhance the detection of early-stage disease and the clinical evaluation of neurobiological features of pathology (e.g. plaque formation as seen in pathologies such as Alzheimer's disease) [11].

 

Many variations and adaptations of MRI are used in brain imaging. Diffusion tensor and diffusion weighted imaging is useful in the evaluation of traumatic brain injury [12]. Both T1- and T2-weighted images are relevant to the study of neurodegenerative diseases such as Alzheimer's disease. Other MRI-related techniques used in neuropathology include:

 

  • Fluid Attenuated Inversion Recovery (FLAIR): This is a pulse-sequence developed to nullify the appearance of fluids when implemented in conjunction with MRI. Therefore, FLAIR can prevent unwanted occlusions by CSF in some images. Hyperintensities in response to FLAIR are thought to be associated with edema in patients with traumatic brain injuries [12].
  • Gradient-Recalled Echo (GRE): The GRE sequence results in echo refocusing that is typically less than 90º. This may allow for shorter scan times, but may be at risk of increased artifacts. GRE may be applied to 2D or 3D scans. It is thought to enhance the appearance of hemorrhages resulting from trauma [12].
  • Susceptibility Weighted Imaging (SWI): This form of imaging is also based on echo gradients, and on the differences in 'magnetizability' between individual tissues. Therefore, it is also regarded as effective in the detection of hemorrhages [13]. The properties of SWI may also be particularly effective in the detection of risk factors associated with complications of an increased middle cerebral artery (MCA) infarction [14].

 

SWI-generated image at 4T showing the venous system of the brain

Figure 1. SWI-generated image at 4T showing the venous system of the brain. Courtesy: SBarnes - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons - https://en.wikipedia.org/wiki/Susceptibility_weighted_imaging#/media/File:SWI_4Tesla.png.

 

The images below should emphasize how different forms of MRI may be best suited to detecting different forms of pathology or tissue. The choice of technique may be informed by medical history, symptoms or the need to assess risk factors for future complications as above.

 

 

An MCA infarctiondetected by DWI

Figure 2 (above). An MCA infarction (red arrows) detected by DWI, as opposed to prominent vessel sign (a marker of infarct growth risk) detected by SWI (white arrows (cortical & medullary veins) & arrowhead (thalamostriate vein)) at the basal ganglion and suprabasal ganglion levels. IC: internal capsule; L: lentiform nucleus; C: caudate nucleus; M3, M4, and M5: zones M3-5 of the MCA. Courtesy: Chen, C.Y., et al., Prominent Vessel Sign on Susceptibility-Weighted Imaging in Acute Stroke: Prediction of Infarct Growth and Clinical Outcome. PLoS One, 2015. 10(6): p. e0131118.

 

Comparision of the suitability of conventional MRI, (T1) FLAIR and SWI in the detection of a microbleed

Figure 3. This image compares the suitability of conventional MRI, (T1) FLAIR and SWI in the detection of a microbleed (arrow). Courtesy: Sharp, D.J. and P.O. Jenkins, Concussion is confusing us all. Pract Neurol, 2015. 15(3): p. 172-186.

 

Traditionally, MRI images are generated in two-dimensional 'slice' form, which may give a certain amount of information about a brain region best highlighted by a particular slice. However, three-dimensional MRI scans are an increasingly common amenity. These scans may offer a more accurate idea of acute damage across more of the surface area of a particular region. Voxel- (or 'volumetric pixels') based images may also highlight volumetric changes in certain brain regions, e.g. in cases of neurodegeneration or chronic trauma. Modern MRI analysis may also generate color-coded images, in which color changes indicate variations in the properties an MR-technique is based on or designed to highlight, e.g. DTI images may show the direction of water diffusion [5].

 

A DW-generated image, color-coded to reveal structures based on the direction of water diffusion.

Figure 4. A DW-generated image, color-coded to reveal structures based on the direction of water diffusion. Courtesy: Sharp, D.J. and P.O. Jenkins, Concussion is confusing us all. Pract Neurol, 2015. 15(3): p. 172-186.

 

Functional MRI is the addition of perfusion to MRI techniques. This may give an enhanced image of CBF and relative cerebral blood volume (rCBV). These values may be affected by the presence of pathologies such as brain tumors [15].

 

Positron Emission Tomography (PET)

 
Positron Emission Tomography is a form of imaging often based on the detection of emissions from radioactive tracer compounds, which may be injected into the CNS. These are most often fluorine isotopes conjugated to simple molecules such as glucose (e.g. [18F]-2-deoxy-2-fluoro-D-glucose (18FDG). As glucose is the primary fuel source of brain cells, tracking the uptake of these compounds with PET results in the robust quantification of brain activity. Reductions in this activity may indicate pathology such as Alzheimer's disease [16]. These changes, as detected with PET-FDG, have been correlated with cognitive discrepancies in studies validating this technique in the detection of CNS disorders [16]. Tracers can be adapted to indicate the presence of specific proteins or other molecules specific to individual pathologies and conditions (as in the 'Alzheimer's Disease' section below). For example, the tracer [11C](R)PK11195 can bind to activated microglia, which is a marker of the inflammatory response to traumatic brain injury [17]. A recent longitudinal study indicated that microglia can remain activated in the brain of a patient for as long as 17 years after such an event [17].

 

The ability to generate radiographic images so relevant to molecules and cells in the tissues of interest is valuable to neurologists. However, PET is susceptible to attenuation. This has given rise to some quantitative bias based on the reduced ability to remove bone signals from PET-generated images. Attenuation may be accounted for using attenuation maps, usually delivered by a different modality such as CT [18]. However, a map generated by MRI resulted in a significant improvement in attenuation correction compared to CT in a recent study [18].

 

 

Common Pathologies of the Brain

 

Alzheimer's Disease (AD)

 

This condition is a form of neurodegeneration, or one in which brain material is damaged and/or dies progressively, giving the appearance of brain tissue that is shrinking (or undergoing atrophy) over time. AD tends to affect cortical, temporal and hippocampal regions. The hippocampus is a roughly horn-shaped structure in the medial temporal lobe, associated with the consolidation of short-term memory into long-term memory [4]. The main 'body' is most often located at a level just above the brainstem in axial sections, from where it curves up and then forwards until it interfaces with the rest of the limbic system. On coronal sections, it may appear vaguely triangular. This brain region is bilateral, or normally appearing on both sides of the brain.

 

 

A coronal MRI showing the hippocampi, with one highlighted in red.

Fig. 5. A coronal MRI showing the hippocampi, with one highlighted in red. Courtesy:  Amber Rieder, Jenna Traynor - Own work. Licensed under CC0 via Wikimedia Commons - https://commons.wikimedia.org/wiki/File:MRI_Location_Hippocampus_up..png#/media/File:MRI_Location_Hippocampus_up..png.

 

The role of imaging in AD is mostly that of evaluating the course and scale of this atrophy. This quantification of atrophy rates may help to estimate the probable effect of AD on the prognosis of the patient, and to evaluate a patient's response to treatment. The effects of AD typically include progressive memory loss and cognitive defects. Less common symptoms of AD include behavioral and emotional abnormalities. These may include increased or unusual levels of apathy, distress and/or irritability [19]. Some patients may also experience motor control anomalies [19]. The appearance of these signs depends on which brain regions are affected by degeneration, and to what extent the atrophy has progressed. AD is prevalent among more senior individuals, although cases among relatively young patients are increasing in number [10].

 

AD may be visualized on whole-brain scans, such as MR-generated images. These may be axial or coronal images of the entire brain. Neurodegeneration as a result of advanced AD is often patently visible on these images. In other words, a temporal or cortical region in one half of the brain may appear to have atrophied markedly in comparison to that of the other [20].

 

Visualization of AD

 

As mentioned above, MRI is often used to evaluate the progression and severity of atrophy as a result of AD [20]. This may be quantified in terms of gross discrepancies in brain matter, and in more specific anatomical features that arise as a result of these. These may include the widening of the choroid fissure, and changes in the dimensions of the lateral ventricle. The temporal horn of this structure is often seen to widen in cases of medial temporal lobe atrophy. These are related to loss of volume in the hippocampus. Cortical atrophy may be detected early on through increased dilation of the sulci [4]. More advanced forms of this may be indicated by the volumetric reduction of gyri [4]. Other anatomical changes that may inform a diagnosis of AD include the enlargement of the perihippocampal fissure. This structure is located lateral to the hippocampus; therefore, deformation of this fissure often indicates this form of neurodegeneration (in combination, again, with reductions in hippocampal volume) [21]. This feature may also be detected using CT- or MR-generated images [21].

 


Figure 6. Two  slices of a T1-weighted MR-generated image, showing an initial scan (left) and the results of a five-month follow-up study of an  elderly patient diagnosed with AD. Note the distinct temporal lobe atrophy (i.e. loss of density) and increases in the size of the lateral ventricles.  Case courtesy of Dr Bruno Di Muzio, Radiopaedia.org. From the case rID: 37720

 

SPECT is regarded as a viable method of detecting earlier signs of AD. These include reduced regional CBF, which occurs mainly in the cerebellum [10]. Patients in the earlier stages of this condition have exhibited reduced CBF in prefrontal, parietal and cingulate regions compared to healthy age-matched controls in studies on the role of SPECT in AD imaging [10]. SPECT imaging studies have also suggested that behavioral changes in patients with AD are also associated with reduced CBF in these regions and in the orbitofrontal cortex [19]. As mentioned above, PET may detect reductions in regional brain metabolic activity that may be associated with the onset of AD. This technique may detect additional molecular signs of this pathology.

 

The neurodegeneration associated with AD is currently thought to result from damage caused by accumulations of dysfunctional and malformed proteins produced by brain cells in the affected regions. These produce some neurobiological hallmarks of the condition, including beta-amyloid plaques and neurofibrillary tangles. State-of-the-art PET tracers are isotopes (most often 18F or 11C) conjugated to molecules that can integrate into these anomalies, thus revealing their locations to an increasingly precise degree when visualized [22]. These tracers have demonstrated effective uptake and integration into neurofibrillary tangles, thus allowing accurate and region-specific detection of brain tissue at risk of atrophy [22]. Classic examples of these neurodegeneration-specific tracers include Pittsburgh compound B, (PiB) which binds to the amyloid protein [10]. PiB-PET has shown improved visual sensitivity compared to FDG-PET in a study involving 62 AD patients and two investigators blinded to their diagnosis [23]. On the other hand, FDG-PET demonstrated better quantitative specificity (98% in comparison with 83% for PiB-PET) [23]. Scans with PiB are deemed 'positive' if tracer binding is more successful in cortical gray matter compared to white matter [21].

 

PET-generated image comparing the binding of PiB in the brain of a patient with AD with that in a control.

Figure 7. PET-generated image comparing the binding of PiB in the brain of a patient with AD with that in a control. Courtesy: Klunkwe - Own work. Licensed under CC SA 3.0 via Wikimedia Commons - https://en.wikipedia.org/wiki/Pittsburgh_compound_B#/media/File:PiB_PET_Images_AD.jpg

 

 

Treatment of AD

 

Conventional forms of therapy for this condition include cholinesterase inhibitors, such as donepezil, rivastigmine and galantamine [24]. These drugs are administered to maintain and/or attenuate cognitive function and also to alleviate behavioral anomalies for some patients [24]. As the name suggests, this is thought to result from an increase of acetylcholine and of nicotinic receptor modulation in cortical regions [19]. A review of clinical trials conducted to validate the effects of these drugs found that cognitive effects in patients were significant for all three [24]. These drugs, at varying dose-regimens, were also found to affect functional status with the exception of donepezil at 5mg daily [24]. Only donepezil and galantamine were found to have effects on behavioral symptoms [24]. A 24-week open-label trial assessed galantamine therapy in patients resistant to treatment with donepezil. The study found that this treatment resulted in significant improvements in the Neuropsychiatry Inventory Brief Questionnaire Form scores for behavioral and motor symptoms [19]. This suggests that galantamine may be superior to donepezil in eliciting improvements in frontal and prefrontal CBF [19]. Cholinesterase inhibitors are associated with a relatively high rate of discontinuation due to side-effects, however [24].

 

Memantine is another drug commonly used in the treatment of AD. This option is an NMDA antagonist associated with similar clinical effects to cholinesterase inhibition [24]. A review of studies, some of which compared memantine to the drugs as above, found it had significant effects on cognition, but tended to be less effective than cholinesterase inhibitors [24]. This review found that memantine, unlike the drugs as above, also had no effect on the clinical Global Impressions of Change scale [24]. However, memantine may be associated with a lower incidence of discontinuation and adverse effects compared to cholinesterase inhibitors [24]. Novel therapeutics and applications in Alzheimer's disease treatment are also being developed. Some are proposed based on the theory concerning the roles of inflammation and reactive nitrogen species in AD [25, 26]. Stem cell therapy is also suggested as a future form of AD treatment [27].

 

Enzymatic therapy, or the administration of drugs such as neprilysin that can break down the beta-amyloid protein in the brain, has shown some promise, but is far from being implemented as standard therapy [28]. The intranasal administration of insulin is also proposed as a new therapy in this condition. This is based on observations by some researchers that brain insulin receptor activity and insulin levels, (which affect regions such as the hippocampus) as well as CSF insulin levels, are decreased in patients with AD compared to controls [29]. Some (albeit small-scale and pilot) clinical studies have claimed beneficial effects on memory and cognition for patients with AD or mild cognitive impairments [29]. An FDG-PET study demonstrated reduced metabolic activity in the frontal, temperoparietal and cingulate regions of people with insulin resistance or type II diabetes compared to healthy controls [30]. Other current forms of therapy that may be recommended to patients include psychotherapy, pharmacotherapy for depressive and behavioral symptoms and occupational therapy such as music therapy or cognitive skills training.

 

 

Glioma


A glioma is a tumor that develops from certain types of brain cells. These glial cells, or glia, are present in nearly all regions of the brain. Their function is the 'maintenance' of the cells that transmit and process information, i.e. neural cells. Gliomas are the most common form of brain cancer, accounting for approximately 80% of all adult brain tumors. 90% of new brain tumors that develop in adults of 45 years or more are found to be gliomas [31]. The study and diagnostic analysis of gliomas can be challenging. This is due to the various subtypes of glia, the classification of tumors into severity grades, and the characteristics of these grades [32]. Current classification guidelines categorize gliomas from grade II (small or low-grade tumors) to grade IV (glioblastoma multiforme, or large metastatic glioma). Defining the grade of a tumor may be important in terms of outcome and treatment options [32].

 

Grade II gliomas often arise from astrocytes, which are present to provide nerve cells with some nutrients and structural support, or oligodendrocytes, which produce the protective neural myelin sheath. Grade II tumors are most often benign, and are growths that retain the characteristics of abnormal glia [33]. Grade III tumors, on the other hand, are more advanced tumors in which the cells have lost the appearance of the glial cell from which they have arisen. These cells have a more uniform appearance that does not conform to the orientation of other normal cells around it. This allows the tumor to increase in mass more easily, and to extend further outwards into other brain regions [33]. The next stage, grade IV, is also malignant, and is associated with necrosis [33]. These tumors are also known as glioblastoma multiforme, and may be highly metastatic. Grade II gliomas are associated with the best rates of survival of all three, and grade IV with the worst [31]. However, grade II tumors are highly recurrent, and may progress to grade III on recurrence [31].

 

Visualization of Gliomas

 

Conventional MRI is indicated as a standard in the regular evaluation of tumor progression and response to treatment [32]. It is also the main technique with which the grading of glioma was established [33]. However, some researchers argue that this technique is not sufficiently sensitive in categorizing some tumor types into grades. MR-generated images of glioma are typically done using gadolinium chelates for contrast. Grade II tumors are typically detected on MRI through the lack of T1-weighted enhancement [32]. If contrast enhancement is present, this may be associated with neovascularization, and thus malignancy [32]. However, the lack of enhancement does not rule out malignancy in all cases [34]. A study of 314 patients with both low-grade and malignant gliomas found that a third of those that did not exhibit contrast enhancement were malignant [34]. Similarly, necrosis may be present in tumors found to be of grade III [32]. MR spectroscopy, in which conventional MRI is combined with the analysis of specific biochemical markers of disease, is also useful in distinguishing malignant glioma from benign growths. A study of 36 patients with tumors diagnosed through histopathology showed that various markers, including N-acetylaspartate, choline, alanine and lipid levels differed significantly between benign and metastatic tumors [35]. Another study of 39 pre-operative patients with varying grades of glioma found that the ratio of choline to creatine, analyzed by MR-spectroscopy, differed significantly between grade II and III tumors. Some research also indicates that the apparent diffusion coefficient (ADC) of tumor cores contributed to accurate grading, but not enhanced differentiation between glioma types of the same grade [35].

 

PET-generated images may also illustrate tumor progression, and possibly distinguish between tumors, through the use of tracers adapted for markers of neoplastic cell proliferation [32]. A PET study incorporating such a tracer ([18F]-fluoro-L-thymidine) showed that the mean and maximum values of its uptake correlated well with differences in grade [32]. Some studies have shown the value of functional MRI in assessing glioma and its grade [32]. A study including 25 patients with high-grade tumors and 39 with lower-grade glioma found that rCBV and rCBF values correlated with tumor grade [15]. However, the values for relative percentage signal intensity recovery (rPSR) were more sensitive and specific (with scores of 96% and 71.8% respectively) than either [15]. Some researchers assert that DWI can improve the specificity and sensitivity of MRI in certain settings, despite its limited success in outcome prediction [35]. On the other hand, ADC maps can be computed from DWI [32].


Fig.8 (above). T2-weighted MR-generated image of a grade ii glioma, which infiltrate the left insular cortex, medial part of left temporal lobe, left lentiform and caudate nuclei as well as left thalamus, albeit without distortion of these structures. Case courtesy of Dr Ahmed Abd Rabou, Radiopaedia.org. From the case rID: 36657

.

 

Fig. 9 (above). MR spectroscopy of the glioma seen in fig. 8. The leftmost image shows the lesion in terms of the ratios of NAA and Cho to Cr; the middle and right images show areas with increased NAA and Cr respectively. Case courtesy of Dr Ahmed Abd Rabou, Radiopaedia.org. From the case rID: 36657

 

Fig. 10 (above). Corresponding T1-generated sagittal image of the glioma (arrows) as also seen in fig. 8 and 9. Case courtesy of Dr Ahmed Abd Rabou, Radiopaedia.org. From the case rID: 36657

 

 

Treatment of Glioma

 

Conventional treatment for glioma includes standard chemotherapy drugs, which are administered to induce cell death in tumors by a variety of biochemical pathways [36]. Chemotherapy for this condition typically involves well-established options such as doxorubicin [36]. However, the formulation of drugs indicated for glioma may feature the addition of molecular structures designed for more efficient passage through the BBB and/or uptake into glial tumors. An example of these is the addition of non-PEGylated liposomes [36]. Other applications designed to permeate the BBB while conveying chemotherapy drugs across it include gold nanoparticles [37]. Treatment with doxorubicin conjugated to these has been reported to result in significantly improved survival compared to doxorubicin alone [37].  

 

High-grade gliomas are particularly resistant to treatment [38]. A prospective study found that the breast cancer drug tamoxifen was able to induce cell death in a sample of human glioma cells, mainly through the induction of oxidative stress [38]. (Oxidative stress is a process in which cells or biological molecules become damaged due to exposure to disproportionate concentrations of reactive oxygen species (ROS). These are present as by-products of natural oxygen metabolism, but may become overproduced in pathological conditions [39].) An animal study incorporating the tamoxifen analog tesmilifene found that this drug was capable of crossing the BBB to increase extravasation in an experimentally-induced tumor [40]. This may represent future drug-therapy options in the treatment of glioma.

 

 

Huntington's Disease

 

Huntington's disease is another form of neurodegeneration. This pathology is associated with the presence of excessive levels of mutant huntingtin, a protein expressed as a result of a genetic mutation. This condition is rare, with an incidence of approximately 0.4 new cases a year per 100,000 [41]. However, it may mimic the symptoms of AD [41]. This is due to its effects on brain regions similar to those affected by AD. Unlike AD, however, advanced Huntington's may result in chorea, or pronounced motor abnormalities that may appear as uncontrollable rhythmic shaking [42]. Huntington's may also affect further brain regions, including the caudate, lateral prefrontal and dorsolateral prefrontal regions [43]. This may influence the probability of additional effects on the emotional status of patients.

 

Imaging of Huntington's

 

MRI studies have shown that patients with Huntington's exhibit significant reductions in functional connections between the anterior cingulate and lateral prefrontal cortex [42]. This may explain the cognitive decline seen in patients with this condition [42]. On the other hand, patients with Huntington's may show increased activity in regions such as the caudal anterior cingulate gyrus, left middle frontal gyrus, and left superior parietal lobule and right dorsal premotor cortex to 'compensate' for this lack of connectivity [42].

 

Treatment of Huntington's

 

Currently, there are few effective pharmacotherapies to attenuate or alleviate the effects of neurodegeneration for patients with this condition. Rehabilitative therapies have shown some success in alleviating volume reduction in the dorsolateral PFC and right caudate [43].

 

Discussion

 

This article outlines information on the many different applications of imaging in neuropathology. It may also offer some guidance on which technique may be used depending on the pathology presented or suspected. Imaging is an efficient and relatively convenient method of detecting the nature and location of an anomaly, especially in a primary or emergency medical setting. Advancements in CT, MRI and PET offer increasingly well-detailed and information-rich images from which an adequately-skilled observer can often estimate disease severity and prognosis.

 

It can be argued that other diagnostic methods may trump imaging in some cases. Histopathology and/or genetic analysis may generate more information on disease progression, disease severity and even on probable response to treatment. For example, analysis of the oncogene BRAF (which codes for B-raf, a protein involved in the regulation of mitosis) can detect the presence of pre-grade II glioma [44]. Unfortunately, these procedures require biopsy and possibly even tumor resection for effect [32]. On the other hand, PET tracers may be adapted to bind an increasing range of biomarkers, and may with further development rival diagnostic histology. PET and SPECT have also been applied to the study of serotonin receptor function and disorder, through the development of tracer-bound serotonin antagonists [9]. Another disadvantage of imaging is that one modality alone may be susceptible to bias due to signal noise, the inability to nullify fluids and lack of tissue differentiation. However, as seen in many instances included in this article, the combination of two or more techniques may overcome this limitation. The use of these is known as multimodal imaging, and may become an increasingly available standard in the near future. These techniques, as outlined above, can complement each other to detect the effects of a single pathology on different tissue types.

 

Conclusion

 

Diagnostic imaging is a multifaceted asset to the study and analysis of neuropathology. Techniques such as CT, MRI and PET can be used alone or in conjunction to produce brain images that are relatively easy to interpret and rate. Some researchers argue that more up-to-date variations on these modalities produce images with higher resolution, reduced noise and enhanced reconstruction. On the other hand, some studies have shown the value of standard CT and MRI in the first-line detection and evaluation of several pathologies.

 

This article has also outlined the role of imaging in the diagnosis of some common brain pathologies. These pathologies may exhibit different diagnostic criteria at different stages of their progression. Imaging can distinguish between these stages. For example, different variations of MRI may differentiate between different grades of glioma. It is also commonly used in the long-term follow-up or study of this pathology type. Therefore, the techniques and modalities used to track the outcome of an individual patient may need to change over time. Certain forms of imaging can also highlight the early or warning signs of some forms of neurodegeneration. Therefore, the imaging hardware and resources available are important points in delivering assessment and treatment.

 

The role of an R.T. includes that of adding to their education on the diagnostic and structural features of various pathologies. This may inform their management and supply of the equipment, techniques and modalities relevant to the discipline of imaging.

 

 

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