The aim of this study was to evaluate the clinical utility of arterial spin labeling (ASL) magnetic resonance imaging (MRI) for the detection of cerebellar hypoperfusion in patients with spinocerebellar degeneration (SCD). Regional cerebral blood flow (CBF) were obtained from ASL and I-IMP single-photon emission computed tomography (SPECT) images by volume-of-interest analysis in patients with SCD (n = 16). Regional CBF were also measured by ASL in age-matched controls (n = 19) and by SPECT in separate controls (n = 17). The cerebellar CBF values were normalized to the CBF values for the whole gray matter (nCBF) in ASL and SPECT. The mean cerebellar nCBF measured by ASL was lower in patients with SCD (0.70 ± 0.09) than in the controls (0.91 ± 0.05) (p < 0.001), which was consistent with the comparison using SPECT (0.82 ± 0.05 vs. 0.98 ± 0.05, p < 0.001). The cerebellar nCBF measured by ASL significantly correlated with that determined by SPECT in patients (r = 0.56, p < 0.001). ASL imaging showed decreased cerebellar blood flow, which correlated with that measured by SPECT, in patients with SCD. These findings suggest the clinical utility of noninvasive MRI with ASL for detecting cerebellar hypoperfusion in addition to atrophy, which would aid the diagnosis of SCD.
The serotonin subtype-4 (5-HT ) receptor, which is known to be involved physiologically in learning and memory, and pathologically in Alzheimer's disease, anxiety, and other neuropsychiatric disorders-has few radioligands readily available for imaging in vivo. We have previously reported two novel 5-HT receptor radioligands, namely [methoxy- C](1-butylpiperidin-4-yl)methyl 4-amino-3-methoxybenzoate; [ C]RX-1), and the [ F]3-fluoromethoxy analog ([ F]RX-2), and in this study we evaluated them by PET in rhesus monkey. Brain scans were performed at baseline, receptor preblock or displacement conditions using SB 207710, a 5-HT receptor antagonist, on the same day for [ C]RX-1 and on different days for [ F]RX-2. Specific-to-nondisplaceable ratio (BP ) was measured with the simplified reference tissue model from all baseline scans. To determine specific binding, total distribution volume (V ) was also measured in some monkeys by radiometabolite-corrected arterial input function after ex vivo inhibition of esterases from baseline and blocked scans. Both radioligands showed moderate to high peak brain uptake of radioactivity (2-6 SUV). Regional BP values were in the rank order of known 5-HT receptor distribution with a trend for higher BP values from [ F]RX-2. One-tissue compartmental model provided good fits with well identified V values for both radioligands. In the highest 5-HT receptor density region, striatum, 50-60% of total binding was specific. The V in receptor-poor cerebellum reached stable values by about 60 min for both radioligands indicating little influence of radiometabolites on brain signal. In conclusion, both [ C]RX-1 and [ F]RX-2 showed positive attributes for PET imaging of brain 5-HT receptors, validating the radioligand design strategy. Synapse 68:613-623, 2014. © 2014 Wiley Periodicals, Inc.
Crossed cerebellar hyperperfusion (CCH) is detected in patients with epilepsy by brain perfusion studies including single photon emission computed tomography and positron emission tomography. In addition, brain perfusion can be studied with arterial spin labeling (ASL), which is a non-invasive MRI perfusion method that quantitatively measures cerebral blood flow per unit tissue mass. We followed up a 47-year-old patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) by continuous arterial spin labeling technique, which showed crossed cerebellar hyperperfusion after acute stroke-like episode. This cerebellar hyperperfusion normalized in the follow-up.
Of the two F-labeled PET ligands currently available to image metabotropic glutamate receptor 5 (mGluR5), [F]FPEB is reportedly superior because [F]SP203 undergoes glutathionlyation, generating [F]-fluoride ion that accumulates in brain and skull. To allow multiple PET studies on the same day with lower radiation exposure, we prepared [C]FPEB and [C]SP203 from [C]hydrogen cyanide and compared their abilities to accurately quantify mGluR5 in human brain, especially as regards radiometabolite accumulation. Genomic plot was used to estimate the ratio of specific-to-nondisplaceable uptake ( BP) without using a receptor blocking drug. Both tracers quantified mGluR5; however [C]SP203, like [F]SP203, had radiometabolite accumulation in brain, as evidenced by increased distribution volume ( V) over the scan period. Absolute V values were ∼30% lower for C-labeled compared with F-labeled radioligands, likely caused by the lower specific activities (and high receptor occupancies) of the C radioligands. The genomic plot indicated ∼60% specific binding in cerebellum, which makes it inappropriate as a reference region. Whole-body scans performed in healthy subjects demonstrated a low radiation burden typical for C-ligands. Thus, the evidence suggests that [C]FPEB is superior to [C]SP203. If prepared in higher specific activity, [C]FPEB would presumably be as effective as [F]FPEB for quantifying mGluR5 in human brain.
This study sought to precisely evaluate striatal oxidative stress and its relationship with the disease severity in Parkinson's disease (PD) using double brain imaging, 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) (62Cu-ATSM) PET and 123I-FP-CIT SPECT. Nine PD patients were studied with brain 62Cu-ATSM PET for oxidative stress and 123I-FP-CIT SPECT for the density of striatal dopamine transporter. Standardized uptake values (SUVs) were obtained from the delayed phase of dynamic 62Cu-ATSM PET, and striatum-to-cerebellum SUV ratio (SUVR) was calculated. To correct the effect of neuronal loss in the striatum, 62Cu-ATSM SUVR was corrected for striatal specific binding ratio (SBR) values of 123I-FP-CIT (SUVR/SBR). 62Cu-ATSM SUVR without correction was not significantly correlated with disease severity estimated by the Unified Parkinson's Disease Rating Scale (UPDRS) scores or 123I-FP-CIT SBR. In contrast, the SUVR/SBR showed significant correlations with the UPDRS total and motor scores, and 123I-FP-CIT SBR. Oxidative stress in the remaining striatal dopaminergic neurons estimated by SUVR/SBR was increased with disease severity in PD patients, suggesting that oxidative stress based on mitochondrial dysfunction contributes to promoting dopaminergic neuronal degeneration in PD. 62Cu-ATSM PET with 123I-FP-CIT SPECT correction would be a promising tool to evaluate dopaminergic neuronal oxidative stress in PD.