Positron Emission Computed Tomography/Single Photon Emission Computed Tomography in Parkinson Disease
Parkinson disease (PD) is the second-most common neurodegenerative disorder, characterized by the selective degeneration and loss of dopaminergic neurons in the substantia nigra pars compacta. This degeneration is primarily caused by the abnormal deposition of Lewy bodies, which leads to a significant reduction in dopamine levels. Positron emission computed tomography (PET) and single photon emission computed tomography (SPECT) are advanced molecular imaging technologies that can directly or indirectly reflect changes at the molecular level by using specific tracers. These imaging techniques have become invaluable tools in PD research, aiding in early diagnosis, disease severity evaluation, clinical manifestation analysis, differential diagnosis, and the exploration of pathological mechanisms.
Introduction to Parkinson Disease and PET/SPECT Imaging
PD is a prevalent neurodegenerative disease, particularly affecting individuals over the age of 65, with a prevalence of 1700 per 100,000 in China. The clinical manifestations of PD are divided into motor and non-motor symptoms. Motor symptoms include bradykinesia, rest tremor, rigidity, and postural instability, while non-motor symptoms encompass rapid eye movement (REM) sleep behavior disorder (RBD), autonomic nervous dysfunction, mental symptoms, and cognitive decline. The diagnosis of PD currently relies heavily on clinical manifestations, which can lead to misdiagnosis, especially in the early stages of Parkinsonism-plus syndrome. Therefore, the development of objective biomarkers is crucial.
PET and SPECT imaging technologies utilize specific tracers to localize and quantify molecular changes, providing insights into the disease’s progression at a molecular level. In PD, the degeneration of dopaminergic neurons in the substantia nigra and the abnormal deposition of Lewy bodies result in decreased dopamine levels in the striatum. Various tracers have been developed to study these changes, including pre-synaptic dopamine transporter (DAT) tracers like 11C-CFT and 99mTc-TRODAT-1, post-synaptic dopamine receptor (DR) tracers such as 11C-raclopride and 123I-IBZM, and intra-synaptic enzyme tracers like 18F-DOPA and 11C-DTBZ.
Early Diagnosis of PD Using PET/SPECT Molecular Imaging
Early diagnosis of PD is challenging because clinical symptoms become apparent only after significant neuronal loss has occurred. PET and SPECT imaging, particularly with DAT tracers, have shown promise in early PD diagnosis. Studies have demonstrated that DAT tracers can detect reductions in dopamine levels before clinical symptoms manifest. For instance, 11C-DTBZ PET has a sensitivity and specificity of 92.9% and 92%, respectively, for PD diagnosis. Similarly, 123I-FP-CIT SPECT studies have shown that DAT decreases in the putamen and caudate nucleus, with the posterior putamen being more severely affected. This stepwise decrease from the posterior to the ventral putamen is a significant indicator of PD.
Evaluation of Disease Severity via PET/SPECT Molecular Imaging
The severity of PD is often evaluated using the Hoehn-Yahr staging system. PET and SPECT imaging can quantitatively assess disease severity by measuring DAT binding rates. Studies have found a negative correlation between DAT binding rates and the severity of motor symptoms. For example, 99mTc-TRODAT-1 SPECT has shown that lower DAT binding rates are associated with more severe motor symptoms. Additionally, patients with the lowest DAT intake are more likely to develop cognitive impairment and mental disorders, indicating a poor prognosis. Therefore, DAT PET/SPECT imaging can serve as a potential biomarker for evaluating PD severity.
Clinical Manifestations and PET/SPECT Imaging
Motor Symptoms
The motor symptoms of PD, including bradykinesia, rest tremor, rigidity, and postural instability, are primarily caused by dopamine deficiency in the striatal system. PET and SPECT imaging have revealed that specific motor symptoms correlate with DAT reductions in particular brain regions. For example, the posterior putamen is often the first area affected in PD patients, and severe dopamine loss in this region is associated with postural instability and gait disorder (PIGD) type PD.
Non-Motor Symptoms
Non-motor symptoms such as RBD, autonomic dysfunction, depression, cognitive decline, and hyposmia are also prevalent in PD. PET and SPECT imaging have been used to explore the relationship between these symptoms and dopamine levels. For instance, patients with PD and RBD show significant dopamine loss, and DAT SPECT imaging can track biochemical changes in these patients. Similarly, studies have found that constipation in early PD is related to decreased DAT binding in the striatum, while depression in PD is associated with reduced DAT binding in the caudate nucleus and ventral striatum. Cognitive impairment in PD is also linked to decreased DAT binding in the caudate nucleus and putamen.
Differential Diagnosis of PD Using PET/SPECT Imaging
PD and Parkinsonism-plus syndrome share similar clinical manifestations, making differential diagnosis challenging. PET and SPECT imaging, particularly with DAT tracers, have been used to distinguish between these conditions. For example, 18F-FP-CIT PET has shown that DAT reductions in the basal ganglia are more severe in progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) compared to PD. Additionally, 18F-FDG PET can identify specific glucose metabolism patterns in different Parkinsonian syndromes, aiding in differential diagnosis. For instance, PSP is characterized by glucose hypometabolism in the frontal lobe, caudate nucleus, midbrain, and thalamus, while MSA shows hypometabolism in the putamen and cerebellum.
Pathological Studies on PD Using PET/SPECT Imaging
The pathological aggregation of α-synuclein is a hallmark of PD and other neurodegenerative diseases. PET and SPECT imaging have been used to study the role of α-synuclein in PD pathogenesis. For example, studies have shown that α-synuclein aggregation leads to synaptic dysfunction in dopaminergic neurons, resulting in neuronal death. PET imaging with 18F-FP-CIT has demonstrated that DAT reductions occur first at the axon terminals of dopaminergic neurons, consistent with the site of α-synuclein action. Additionally, labial gland biopsies combined with DAT PET imaging have shown that α-synuclein aggregation in the labial gland correlates with DAT changes, providing a potential method for early PD diagnosis.
Conclusion
PET and SPECT imaging technologies have revolutionized the study of PD by providing detailed molecular insights into the disease’s progression. These imaging techniques have been applied to various aspects of PD research, including early diagnosis, disease severity evaluation, clinical manifestation analysis, differential diagnosis, and pathological studies. By utilizing specific tracers, PET and SPECT imaging can detect changes in dopamine levels and other molecular markers, offering valuable information for clinical practice and research. As imaging technology continues to advance, PET and SPECT will likely play an even more significant role in understanding and managing PD.
doi.org/10.1097/CM9.0000000000000836
Was this helpful?
0 / 0