Role of PET and SPECT in the Study of Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis has been defined as a “heterogeneous group of neurodegenerative syndromes characterized by progressive muscle paralysis caused by the degeneration of motor neurons allocated in primary motor cortex, brainstem, and spinal cord.” A comprehensive diagnostic workup for ALS usually includes several electrodiagnostic, clinical laboratory and genetic tests. Neuroimaging exams, such as computed tomography, magnetic resonance imaging and spinal cord myelogram, may also be required. Nuclear medicine, with PET and SPECT, may also play a role in the evaluation of patients with ALS, and provide additional information to the clinicians. This paper aims to offer to the reader a comprehensive review of the different radiotracers for the assessment of the metabolism of glucose (FDG), the measurement of cerebral blood flow (CBF), or the evaluation of neurotransmitters, astrocytes, and microglia by means of newer and not yet clinically diffuse radiopharmaceuticals.

Phosphorylation of Threonine 175 Tau in the Induction of Tau Pathology in Amyotrophic Lateral Sclerosis—Frontotemporal Spectrum Disorder (ALS-FTSD). A Review

“…Neuroimaging platforms such as single positron emission computerized tomography (SPECT) (Neary et al, 1990 ), MRI-based measures of functional connectivity (Douaud et al, 2011 ), and advanced structural MRI sequences that define subcortical frontotemporal white matter tract projection pathology (Agosta et al, 2016 ) can now provide an evaluation of the extent of loss of functional integrity. Positron emission tomography (PET) has proven invaluable in our understanding of the anatomic and cellular extent of the pathobiology of ALS-FTSD, including the involvement of non-neuronal cells in the disease process (Cistaro et al, 2012 , 2014 ). Increasingly, these neuroimaging modalities are being linked to understanding the molecular pathology of ALS, such as the degree of deeper cortical structures and cerebellar pathology evident in those ALS patients carrying pathological hexanucleotide expansions in C9orf72 , even in the presymptomatic stages (Mahoney et al, 2012 ; Bede et al, 2013 ; Rohrer et al, 2015 ; Walhout et al, 2015 ).…”

Prospective Validation of 18F-FDG Brain PET Discriminant Analysis Methods in the Diagnosis of Amyotrophic Lateral Sclerosis

“…In patients with ALS, a pattern of relative hypometabolism in the primary motor cortex, premotor cortices, and supplementary motor cortex but extending to extramotor areas such as the frontal and parietal lobes as well has been observed (2,4,(7)(8)(9)(10)(11). Relative hypermetabolism is observed in the mesotemporal cortex, cerebellum, and upper brain stem (2,4,7,10,(12)(13)(14). Within-center retrospective discriminant analysis methods to differentiate subjects with early ALS from controls have resulted in an overall classification accuracy of 90%-95% (2,4,10).…”

The Molecular Effects of Ionizing Radiations on Brain Cells: Radiation Necrosis vs. Tumor Recurrence

“…In brain cells, glucose metabolism represents the main source of adenosine triphosphate (ATP) required for brain functions, in fact, it is physiologically connected to neuronal activity. More in particular, glucose is transported across BBB by GLUT-1, whereas another transporter, GLUT-3, is responsible for the constant glucose supply to neurons, especially in case of low extracellular levels (i.e., hypoglycemia) [44]. 18 F-FDG ( Figure 1) is a glucose analogue that undergoes the same metabolic pathway as regular glucose but thanks to its binding to 18 F-, 18 F-FDG-6-phosphate cannot be processed further, therefore the distribution of 18 F-FDG reflects glucose uptake distribution and its utilization by cells throughout the body.…”