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This chapter reviews the use of biomarkers, including brain imaging. These techniques have revolutionised dementia research, although their availability for regular clinical practice is still developing. The chapter begins with a review of structural imaging techniques such as CT and MRI, and discusses the use of the dementia evolution scale. Functional techniques such as fMRI, SPECT, and PET are reviewed, including amyloid PET scans, which can identify the presence of beta amyloid protein and its distribution throughout the brain.
This chapter highlights some of the tools used for imaging features of the nervous system. The introduction defines the concepts of temporal and spatial resolution, the anatomical language used to describe structures in relation to one another, and planes of imaging, all of which are knowledge essential to understanding imaging figures. The chapter then describes both structural and functional imaging techniques and the figures that may accompany these scanning methods, including dissection; CT scans; PET scans; various applications of MRI scanning including arterial spin labeling, functional MRI, and diffusion tensor imaging for tract tracing; SPECT scans; and electroencephalography imaging, including a description of event-related potentials.
PET imaging is increasingly recognized as an important diagnostic tool to investigate patients with cognitive disturbances of possible neurodegenerative origin. PET with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), assessing glucose metabolism, provides a measure of neurodegeneration and allows a precise differential diagnosis among the most common neurodegenerative diseases, such as Alzheimer’s disease, frontotemporal dementia or dementia with Lewy bodies. PET tracers specific for the pathological deposits characteristic of different neurodegenerative processes, namely amyloid and tau deposits typical of Alzheimer’s Disease, allow the visualization of these aggregates in vivo. [18F]FDG and amyloid PET imaging have reached a high level of clinical validity and are since 2022 investigations that can be offered to patients in standard clinical care in most of Canada.
This article will briefly review and summarize the current knowledge on these diagnostic tools, their integration into diagnostic algorithms as well as perspectives for future developments.
The use of imaging in epilepsy care is a powerful tool to show a patient why they have epilepsy. You can use it to correlate your semiology history with an imaging finding. Magnetic resonance imaging (MRI) is the most widely used modality for epilepsy care. Ordering an epilepsy protocol MRI on a 3 Tesla (3T) machine increases the likelihood of finding an epilepsy’s etiology. Common findings include stroke, tumor (i.e., ganglioglioma), hippocampal sclerosis, encephalocele, cortical dysplasia, heterotopia, polymicrogyria, or cavernoma. For MRI-negative epilepsy, additional tests to identify the epileptogenic region include PET (positron emission tomography) and SPECT (single photon emission computed tomography). Functional MRI (fMRI) can delineate brain areas critical for specific functions.Lastly, the use of CT (computed tomography) is limited to identification of acute findings like hemorrhage and tumors in new onset seizures.
Functional imaging has been reported to have a limited impact in the diagnosis of insular epilepsies, showing unspecific or misleading features. However, recent studies have demonstrated that PET and SPECT may be helpful in identifying abnormalities pointing to insula and guiding invasive monitoring. FDG-PET may detect a focal or regional hypometabolism in about half of the cases, and its localization value is greatly improved by the coregistration with MRI. In addition, PET may help lateralize the insular seizures, and statistical analysis contributes to differentiate them from temporal and frontal lobe seizures. SEEG strategy benefits from PET findings, as electrode implantation within the main hypometabolic areas improves the concordance rate between the PET pattern and the localization of the epileptogenic zone. Finally, PET is a reliable tool for the detection of insular focal cortical dysplasias, especially in MRI negative cases. These findings are helpful for planning surgery in these difficult-to-treat epilepsies. SPECT regional cerebral blood flow (rCBF) imaging under both interictal and ictal conditions is a mainstay of localization of epileptogenic foci in subjects with medically intractable epilepsy contemplating surgical ablation of disease-causing focal brain anomalies. Its performance is excellent in patients with mesial temporal lobe epilepsy, but neocortical foci remain harder to evaluate, in particular because of their tendency to generalize more rapidly than the former. The specific case of insular epilepsy has been studied in a limited number of studies only, reporting on a few tens of patients overall. Although this limits the possibility of conducting well-powered statistical analysis of the sensitivity and specificity of interictal/ictal SPECT rCBF imaging in this condition, available results converge towards the conclusion that this technique offers useful and important information in the pre-operative assessment of patients afflicted by that often difficult to characterize disease.
Clozapine is the least likely anti-psychotic to induce extrapyramidal symptoms (EPS). We present a surprising case of a woman schizophrenic patient treated with clozapine suffering from EPS. Single photon emission computed tomography (SPECT) revealed a low density of presynaptic dopamine transporters in our patient's brain. A comorbid diagnosis of Parkinson's disease in schizophrenia was confirmed in this way. This helped us to find a proper therapeutic strategy for our patient.
The aim of the present study is to see if the changes in the regional cerebral blood flow (rCBF) experienced by restrictive anorexia nervosa (AR) and bulimia nervosa (BN) patients, following the exposure to their own body image, persist at follow-up.
Methods
Three single photon emission computed tomography (SPECT) were performed on nine patients with a DSM-IV diagnosis of AR, 13 with BP, and 12 controls: at rest, following a neutral stimulus, and after exposure to their previously filmed whole body image. Body dissatisfaction was measured by means of the Body Dissatisfaction Questionnaire (BSQ). One year later the same assessment was repeated.
Results
Following the exposure to their own body image, BN showed an increase in body dissatisfaction, which was associated with the increase in the rCBF of the Right Temporal Area. Those changes persisted at follow-up.
Discussion
More specific long term therapies are needed for the treatment of the averse response showed by ED patients to their own body image exposure that is associated with the hyperactivation of the right temporal area when they are confronted with their whole body image.
Regional cerebral blood flow (rCBF) values were measured by single photon emission computed tomography (SPECT) in different regions of the brain in 27 patients with DAT. Significant correlations were found between rCBF in left parieto-temporooccipital regions and psychometric test scores. Patients with hemisphere asymmetry in SPECT performed worse on psychometric tests. SPECT did not permit prediction of or differentiation between depressive and psychotic symptoms.
Multiple lines of evidence including recent imaging studies suggest that schizophrenia is associated with an imbalance of the dopaminergic system, entailing hyperstimulation of striatal dopamine (DA) D2 receptors and understimulation of cortical DA D1 receptors. This DA endophenotype presumably emerges from the background of a more general synaptic dysconnectivity, involving alterations in N-methyl-d-aspartate (NMDA) and glutamatergic (GLU) functions. Equally important is the fact that this DA dysregulation might further impair NMDA transmission. The first generation antipsychotic (FGA) drugs are characterized by high affinity to and generally high occupancy of D2 receptors. The efficacy of FGAs is limited by a high incidence of extrapyramidal side-effects (EPS). Second generation antipsychotic (SGA) drugs display reduced EPS liability and modest but clinically significant enhanced therapeutic efficacy. Compared to FGAs, the improved therapeutic action of SGAs probably derives from a more moderate D2 receptor blockade. We will review the effects of SGAs on other neurotransmitter systems and conclude by highlighting the importance of therapeutic strategies aimed at directly increasing prefrontal DA, D1 receptor transmission or NMDA transmission to enhance the therapeutic effect of moderate D2 receptor antagonism.
In this study, we evaluated brain perfusion in patients with first-episode medicated schizophrenia using the new analytical method, statistical parametric mapping (SPM) applied to single photon emission computed tomography (SPECT).
Method
We performed SPECT with 99-Tc-ethyl cysteinate dimer (99mTc-ECD) of the brain and magnetic resonance imaging (MRI) in patients with schizophrenia (n = 30) and control subjects matched for age and gender (n = 37). A voxel-by-voxel group analysis was performed using SPM2 (Z > 3.0, P < 0.001, uncorrected for multiple comparisons).
Result
In comparison with control subjects, the volumes of the bilateral frontal areas were found to be decreased on MRI. Blood flow was found to be reduced in the bilateral temporal areas in the patients with schizophrenia on SPECT.
Conclusion
In this study, patients with first-episode schizophrenia appeared to have significant bilateral temporal hypoperfusion, although temporal volumes were not significantly decreased in comparison with control subjects. Abnormality of temporal lobe blood flow in schizophrenia may show that functional changes occur earlier than structural changes, and may assist in the diagnosis of schizophrenia.
Considerable progress has been achieved over the past 15 years in uncovering the biological basis of major psychiatric disorders. Since psychopharmacological treatment is thought tc act on the underlying biological basis of the disease, brain imaging techniques enable us to understand the mechanism of action of such compounds. One important tool used to determine patterns of brain dysfunction and how psychopharmacological agents such as antipsychotic compounds work is single-photon emission computerised tomography (SPECT). This technique allows determination of striatal D2 receptor occupancy rates, which are associated with the extrapyramidal side effects (EPS) of antipsychotic drugs. Studies have confirmed that atypical antipsychotic agents have lower occupancy rates than typical agents. No association has been found between D2 receptor occupancy rates n the striatum and antipsychotic efficacy, and it therefore appears that striatal D2 receptor occupancy rates are not necessary for the antipsychotic effect of such agents in schizophrenia. The availability of more refined radioligands will help us not only to understand the action of antipsychotics but also the pathophysiology of schizophrenia.
This study was performed to investigate the association between the mid-brain serotonin transporter (SERT) availability and intelligence quotient (IQ).
Methods:
One hundred and thirteen healthy participants, including 52 male and 61 female subjects, were recruited. We used SPECT with [123I]ADAM images to determine the SERT availability in the mid-brain, and measured the subjects’ IQ using the WAIS-R.
Results:
We found a significant positive correlation between the mid-brain SERT availability and the IQ of the participants. Even when controlling for age and sex, the significant association still existed.
Conclusion:
This result implied that the higher the SERT binding in the mid-brain, the better the IQ in healthy participants.
Serotonin transporter (SERT) and dopamine transporter (DAT) levels differ in patients with major depressive disorder (MDD) who are in a depressed state in comparison with healthy controls. In addition, a family history of depression is a potent risk factor for developing depression, and inherited vulnerability to serotonergic and dopaminergic dysfunction is suspected in this. The aim of this study was to examine the availabilities of midbrain SERT and striatal DAT in healthy subjects with and without a first-degree family history of MDD.
Methods
Eight healthy subjects with first-degree relatives with MDD and 16 sex- and age-matched healthy controls were recruited. The availabilities of SERT and DAT were approximated using SPECT, employing [123I] 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM) and [99mTc] TRODAT-1 as the ligands, respectively. There are missing data for one participant with a first-degree family history of MDD from the ADAM study, due to a lack of the radio-ligand at the time of experiment.
Results
SERT availability in the midbrain was significantly lower in subjects with a first-degree family history of MDD than in healthy subjects. However, DAT availability was no different between two groups.
Conclusions
The results with regard to the midbrain SERT level suggest the heritability of MDD.
Stimulant drugs can cause persistent changes in the brain. Imaging studies show that these changes are most apparent in dopamine transporter (DAT) or receptor availability within the striatum.
Methods:
This work focuses on influences of stimulant use on dopaminergic function assessed using nuclear-medicine imaging (PET/SPECT). Included are 39 studies on 655 cocaine, amphetamine, methamphetamine or nicotine users, as well as 690 healthy controls. Metaanalyses were conducted separately for D2/D3 receptors and dopamine transporters of the entire striatum, its subregions caudate and putamen respectively.
Results:
Meta-analyses results regarding nicotine did not show significant effects between smokers and nonsmokers. In cocaine users there was a significant decrease in dopamine receptor availability in all regions. The striatal DAT availability was significantly increased in cocaine users. Methamphetamine users showed a significantly decreased dopamine receptor and transporter density in all regions. Significant results also indicate a lower transporter availability in all regions. Amphetamine users showed reduced DAT availability in the striatum, as well as in the sub regions.
Conclusion:
This meta-analysis provides evidence that there are ongoing changes in the dopaminergic system associated with the use of stimulants. Especially the results of cocaine, methamphetamine and amphetamine use mainly showed a downregulation. In addition, this meta-analysis is the first to include nicotine. This subset of studies showed evidence for a decreased receptor and DAT availability but no significant results were found in the metaanalyses.
Psychotic symptoms have been linked to salience abnormalities in the brain reward system, perhaps caused by a dysfunction of the dopamine neurotransmission in striatal regions. Blocking dopamine D2 receptors dampens psychotic symptoms and normalises reward disturbances, but a direct relationship between D2 receptor blockade, normalisation of reward processing and symptom improvement has not yet been demonstrated. The current study examined the association between blockade of D2 receptors in the caudate nucleus, alterations in reward processing and the psychopathology in a longitudinal study of antipsychotic-naïve first-episode schizophrenia patients.
Methods
Twenty-two antipsychotic-naïve first-episode schizophrenia patients (10 males, mean age 23.3) and 23 healthy controls (12 males, mean age 23.5) were examined with single-photon emission computed tomography using 123I-labelled iodobenzamide. Reward disturbances were measured with functional magnetic resonance imaging (fMRI) using a modified version of the monetary-incentive-delay task. Patients were assessed before and after 6 weeks of treatment with amisulpride.
Results
In line with previous results, patients had a lower fMRI response at baseline (0.2 ± 0.5 v. 0.7 ± 0.6; p = 0.008), but not at follow-up (0.5 ± 0.6 v. 0.6 ± 0.7), and a change in the fMRI signal correlated with improvement in Positive and Negative Syndrome Scale positive symptoms (ρ = −0.435, p = 0.049). In patients responding to treatment, a correlation between improvement in the fMRI signal and receptor occupancy was found (ρ = 0.588; p = 0.035).
Conclusion
The results indicate that salience abnormalities play a role in the reward system in schizophrenia. In patients responding to a treatment-induced blockade of dopamine D2 receptors, the psychotic symptoms may be ameliorated by normalising salience abnormalities in the reward system.
In addition to neurocognitive studies, neuroimaging techniques provide a unique opportunity to study brain characteristics. Structural imaging studies clearly demonstrate volumetric differences in particular brain areas between individuals with a history of nonfatal suicidal behavior and those without such a history. Functional imaging studies show a reduced prefrontal perfusion or metabolism and a blunted increase in activation when challenged in the brains of individuals with a history of suicide attempts. Moreover, impairment of the prefrontal serotonergic system in association with suicidal behavior is demonstrated in a number of studies. Recent structural and functional imaging studies show changes in cortical and subcortical areas and their connections in association with suicidal behavior and risk factors such as mental pain, hopelessness, and impulsivity. The global picture that emerges from these studies reflects the involvement of a particular circuit in the development of suicidal behavior, the so-called frontothalamic network.
Our recent single-photon emission computed tomography (SPECT) study of patients with late-onset Alzheimer’s disease (AD) revealed that regional cerebral blood flow (rCBF) was reduced in the frontal, temporal, and limbic lobes, and to a lesser degree in the parietal and occipital lobes. Moreover, these patients’ scores on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) were significantly correlated with rCBF in some gyri of the frontal, parietal, and limbic lobes. Our present study aimed to understand how vascular factors and metabolic disease influenced the relationship between rCBF and ADAS-cog scores.
Methods
We divided late-onset AD patients into two groups according to their Hachinski Ischemic Score (HIS), low vascular risk patients had values of ≤4 (n=25) and high vascular risk patients had scores ≥5 (n=15). We examined rCBF using brain perfusion SPECT data.
Results
The degrees and patterns of reduced rCBF were largely similar between late-onset AD patients in both groups, regardless of HIS values. Cognitive function was significantly associated with rCBF among late-onset AD patients with low vascular risk (HIS≤4), but not among those with high vascular risk (HIS≥5). Furthermore, metabolic diseases, such as hypertension and diabetes mellitus, disrupted the relationships between hypoperfusion and cognitive impairments in late-onset AD patients.
Conclusion
Factors other than hypoperfusion, such as hypertension and diabetes mellitus, could be involved in the cognitive dysfunction of late-onset AD patients with high vascular risk.
Objectives: To examine neuropsychological test performance among individuals clinically diagnosed with Parkinson’s disease (PD) without evidence of dopaminergic deficiency on [123]I-CIT single photon emission computed tomography imaging. Methods: Data were obtained from the Parkinson’s Progression Marker Initiative. The sample included 59 participants with scans without evidence of dopaminergic deficiency (SWEDD), 412 with PD, and 114 healthy controls (HC). Tests included Judgment of Line Orientation, Letter-Number Sequencing, Symbol Digit Modalities, Hopkins Verbal Learning Test-Revised, and Letter and Category Fluency. Multivariate analysis of variance was used to compare standardized scores between the groups. Results: There was a statistically significant difference in performances between the groups, F(14,1155)=5.04; p<.001; partial η2=.058. Pairwise comparisons revealed significant differences in Category Fluency between SWEDD (M=0.22; SD=1.08) and HC (M=0.86; SD=1.15) and in Symbol Digit Modalities Test performance between SWEDD (M=45.09; SD=11.54) and HC (M=51.75; SD=9.79). No significant differences between SWEDD and PD were found. Using established criteria, approximately one in four participants in the SWEDD and PD groups met criteria for mild cognitive impairment (MCI). Conclusions: Individuals with SWEDD demonstrate significantly worse mental processing speed and semantic fluency than HC. The neuropsychological test performances and rates of MCI were similar between the SWEDD group and PD groups, which may reflect a common pathology outside of the nigrostriatal pathway. (JINS, 2018, 24, 646–651)