Geoffrey Warnock

Evaluation of Atlas-Based Attenuation Correction for Integrated PET/MR in Human Brain: Application of a Head Atlas and Comparison to True CT-Based Attenuation Correction

Attenuation correction (AC) for integrated PET/MR imaging in the human brain is still an open problem. In this study, we evaluated a simplified atlas-based AC (Atlas-AC) by comparing 18F-FDG PET data corrected using either Atlas-AC or true CT data (CT-AC). Methods: We enrolled 8 patients (median age, 63 y). All patients underwent clinically indicated whole-body 18F-FDG PET/CT for staging, restaging, or follow-up of malignant disease. All patients volunteered for an additional PET/MR of the head (additional tracer was not injected). For each patient, 2 AC maps were generated: an Atlas-AC map registered to a patient-specific liver accelerated volume acquisition-Flex MR sequence and using a vendor-provided head atlas generated from multiple CT head images and a CT-based AC map. For comparative AC, the CT-AC map generated from PET/CT was superimposed on the Atlas-AC map. PET images were reconstructed from the list-mode raw data from the PET/MR imaging scanner using each AC map. All PET images were normalized to the SPM5 PET template, and 18F-FDG accumulation was quantified in 67 volumes of interest (VOIs; automated anatomic labeling atlas). Relative difference (%diff) between images based on Atlas-AC and CT-AC was calculated, and averaged difference images were generated. 18F-FDG uptake in all VOIs was compared using Bland–Altman analysis. Results: The range of error in all 536 VOIs was −3.0%–7.3%. Whole-brain 18F-FDG uptake based on Atlas-AC was slightly underestimated (%diff = 2.19% ± 1.40%). The underestimation was most pronounced in the regions below the anterior/posterior commissure line, such as the cerebellum, temporal lobe, and central structures (%diff = 3.69% ± 1.43%, 3.25% ± 1.42%, and 3.05% ± 1.18%), suggesting that Atlas-AC tends to underestimate the attenuation values of the skull base bone. Conclusion: When compared with the gold-standard CT-AC, errors introduced using Atlas-AC did not exceed 8% in any brain region investigated. Underestimation of 18F-FDG uptake was minor (<4%) but significant in regions near the skull base.

Posterior cingulate γ-aminobutyric acid and glutamate/glutamine are reduced in amnestic mild cognitive impairment and are unrelated to amyloid deposition and apolipoprotein E genotype

The biomarker potential of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) for the in vivo characterization of preclinical stages in Alzheimers disease has not yet been explored. We measured GABA, glutamate + glutamine (Glx), and N-acetyl-aspartate (NAA) levels by single-voxel MEGA-PRESS magnetic resonance spectroscopy in the posterior cingulate cortex of 21 elderly subjects and 15 patients with amnestic mild cognitive impairment. Participants underwent Pittsburgh Compound B positron emission tomography, apolipoprotein E (APOE) genotyping, and neuropsychological examination. GABA, Glx, and NAA levels were significantly lower in patients. NAA was lower in Pittsburgh Compound B-positive subjects and APOE ε4 allele carriers. GABA, Glx, and NAA levels were positively correlated to CERAD word learning scores. Reductions in GABA, Glx, and NAA levels may serve as metabolic biomarkers for cognitive impairment in amnestic mild cognitive impairment. Because GABA and Glx do not seem to reflect amyloid β deposition or APOE genotype, they are less likely biomarker candidates for preclinical Alzheimers disease.

Clinical evaluation of ZTE attenuation correction for brain FDG-PET/MR imaging—comparison with atlas attenuation correction

Accurate attenuation correction (AC) on PET/MR is still challenging. The purpose of this study was to evaluate the clinical feasibility of AC based on fast zero-echo-time (ZTE) MRI by comparing it with the default atlas-based AC on a clinical PET/MR scanner. Methods: We recruited 10 patients with malignant diseases not located on the brain. In all patients, a clinically indicated whole-body 18F-FDG PET/CT scan was acquired. In addition, a head PET/MR scan was obtained voluntarily. For each patient, 2 AC maps were generated from the MR images. One was atlas-AC, derived from T1-weighted liver acquisition with volume acceleration flex images (clinical standard). The other was ZTE-AC, derived from proton-density-weighted ZTE images by applying tissue segmentation and assigning continuous attenuation values to the bone. The AC map generated by PET/CT was used as a silver standard. On the basis of each AC map, PET images were reconstructed from identical raw data on the PET/MR scanner. All PET images were normalized to the SPM5 PET template. After that, these images were qualified visually and quantified in 67 volumes of interest (VOIs; automated anatomic labeling, atlas). Relative differences and absolute relative differences between PET images based on each AC were calculated. 18F-FDG uptake in all 670 VOIs and generalized merged VOIs were compared using a paired t test. Results: Qualitative analysis shows that ZTE-AC was robust to patient variability. Nevertheless, misclassification of air and bone in mastoid and nasal areas led to the overestimation of PET in the temporal lobe and cerebellum (%diff of ZTE-AC, 2.46% ± 1.19% and 3.31% ± 1.70%, respectively). The |%diff| of all 670 VOIs on ZTE was improved by approximately 25% compared with atlas-AC (ZTE-AC vs. atlas-AC, 1.77% ± 1.41% vs. 2.44% ± 1.63%, P < 0.01). In 2 of 7 generalized VOIs, |%diff| on ZTE-AC was significantly smaller than atlas-AC (ZTE-AC vs. atlas-AC: insula and cingulate, 1.06% ± 0.67% vs. 2.22% ± 1.10%, P < 0.01; central structure, 1.03% ± 0.99% vs. 2.54% ± 1.20%, P < 0.05). Conclusion: The ZTE-AC could provide more accurate AC than clinical atlas-AC by improving the estimation of head–skull attenuation. The misclassification in mastoid and nasal areas must be addressed to prevent the overestimation of PET in regions near the skull base.

Regional cerebral blood flow estimated by early PiB uptake is reduced in mild cognitive impairment and associated with age in an amyloid-dependent manner

Early uptake of [(11)C]-Pittsburgh Compound B (ePiB, 0-6 minutes) estimates cerebral blood flow. We studied ePiB in 13 PiB-negative and 10 PiB-positive subjects with mild cognitive impairment (MCI, n = 23) and 11 PiB-positive and 74 PiB-negative cognitively healthy elderly control subjects (HCS, n = 85) in 6 bilateral volumes of interest: posterior cingulate cortex (PCC), hippocampus (hipp), temporoparietal region, superior parietal gyrus, parahippocampal gyrus (parahipp), and inferior frontal gyrus (IFG) for the associations with cognitive status, age, amyloid deposition, and apolipoprotein E ε4-allele. We observed no difference in ePiB between PiB-positive and -negative subjects and carriers and noncarriers. EPiB decreased with age in PiB-positive subjects in bilateral superior parietal gyrus, bilateral temporoparietal region, right IFG, right PCC, and left parahippocampal gyrus but not in PiB-negative subjects. MCI had lower ePiB than HCS (left PCC, left IFG, and left and right hipp). Lowest ePiB values were found in MCI of 70 years and older, who also displayed high cortical PiB binding. This suggests that lowered regional cerebral blood flow indicated by ePiB is associated with age in the presence but not in the absence of amyloid pathology.

An overview of CEST MRI for non-MR physicists

The search for novel image contrasts has been a major driving force in the magnetic resonance (MR) research community, in order to gain further information on the body’s physiological and pathological conditions.Chemical exchange saturation transfer (CEST) is a novel MR technique that enables imaging certain compounds at concentrations that are too low to impact the contrast of standard MR imaging and too low to directly be detected in MRS at typical water imaging resolution. For this to be possible, the target compound must be capable of exchanging protons with the surrounding water molecules. This property can be exploited to cause a continuous buildup of magnetic saturation of water, leading to greatly enhanced sensitivity.The goal of the present review is to introduce the basic principles of CEST imaging to the general molecular imaging community. Special focus has been given to the comparison of state-of-the-art CEST methods reported in the literature with their positron emission tomography (PET) counterparts.

Quantitative Cerebral Perfusion Imaging in Children and Young Adults with Moyamoya Disease: Comparison of Arterial Spin-Labeling–MRI and H2[15O]-PET

BACKGROUND AND PURPOSE: Cerebral perfusion assessment is important in the preoperative evaluation and postoperative follow-up of patients with Moyamoya disease. The objective of this study was to evaluate the correlation of quantitative CBF measurements performed with arterial spin-labeling–MR imaging and H2[15O]-PET in children and young adults with Moyamoya disease. MATERIALS AND METHODS: Thirteen children and young adults (8 female patients; age, 9.7 ± 7.1 years; range, 1–23 years) with Moyamoya disease underwent cerebral perfusion imaging with H2[15O]-PET (Discovery STE PET/CT, 3D Fourier rebinning filtered back-projection, 128 × 128 × 47 matrix, 2.34 × 2.34 × 3.27 mm3 voxel spacing) and arterial spin-labeling (3T scanner, 3D pulsed continuous arterial spin-labeling sequence, 32 axial sections, TR = 5.5 seconds, TE = 25 ms, FOV = 24 cm, 128 × 128 matrix, 1.875 × 1.875 × 5 mm3 voxel spacing) within less than 2 weeks of each other. Perfusion of left and right anterior cerebral artery, MCA, and posterior cerebral artery territories was qualitatively assessed for arterial spin-labeling–MR imaging and H2[15O]-PET by 2 independent readers by use of a 3-point-Likert scale. Quantitative correlation of relative CBF with cerebellar normalization between arterial spin-labeling–MR imaging and H2[15O]-PET was evaluated in a volume-based approach for each vascular territory after 3D image coregistration. RESULTS: Interreader agreement was good (κ = 0.67–0.69), and strong and significant correlations were found between arterial spin-labeling–MR imaging and H2[15O]-PET for both qualitative perfusion scoring (ρ = 0.77; P < .001) and quantitative perfusion assessment of relative CBF with cerebellar normalization (r = 0.67, P < .001). CONCLUSIONS: In children and young adults with Moyamoya disease, quantitative evaluation of CBF is possible with the use of arterial spin-labeling–MR imaging without ionizing radiation or contrast injection with a good correlation to H2[15O]-PET after cerebellar normalization.

Comparison of PET template-based and MRI-based image processing in the quantitative analysis of C11-raclopride PET

BackgroundQuantitative measures of 11C-raclopride receptor binding can be used as a correlate of postsynaptic D2 receptor density in the striatum, allowing 11C-raclopride positron emission tomography (PET) to be used for the differentiation of Parkinson’s disease from atypical parkinsonian syndromes. Comparison with reference values is recommended to establish a reliable diagnosis. A PET template specific to raclopride may facilitate direct computation of parametric maps without the need for an additional MR scan, aiding automated image analysis.MethodsSixteen healthy volunteers underwent a dynamic 11C-raclopride PET and a high-resolution T1-weighted MR scan of the brain. PET data from eight healthy subjects was processed to generate a raclopride-specific PET template normalized to standard space. Subsequently, the data processing based on the PET template was validated against the standard magnetic resonance imaging (MRI)-based method in 8 healthy subjects and 20 patients with suspected parkinsonian syndrome. Semi-quantitative image analysis was performed in Montreal Neurological Institute (MNI) and in original image space (OIS) using VOIs derived from a probabilistic brain atlas previously validated by Hammers et al. (Hum Brain Mapp, 15:165–174, 2002).ResultsThe striatal-to-cerebellar ratio (SCR) of 11C-raclopride uptake obtained using the PET template was in good agreement with the MRI-based image processing method, yielding a Lin’s concordance coefficient of 0.87. Bland-Altman analysis showed that all measurements were within the ±1.96 standard deviation range. In all 20 patients, the PET template-based processing was successful and manual volume of interest optimization had no further impact on the diagnosis of PD in this patient group. A maximal difference of <5% was found between the measured SCR in MNI space and OIS.ConclusionsThe PET template-based method for automated quantification of postsynaptic D2 receptor density is simple to implement and facilitates rapid, robust and reliable image analysis. There was no significant difference between the SCR values obtained with either PET- or MRI-based image processing. The method presented alleviates the clinical workflow and facilitates automated image analysis.

Relation of dopamine receptor 2 binding to pain perception in female fibromyalgia patients with and without depression – A [11C] raclopride PET-study

Dopamine D2/D3 receptor availability at rest and its association with individual pain perception was investigated using the [(11)C] raclopride PET-method in 24 female Fibromyalgia (FMS) participants with (FMS+, N=11) and without (FMS-, N=13) comorbid depression and in 17 healthy women. Thermal pain thresholds (TPT) and pain responses were assessed outside the scanner. We compared the discriminative capacity, i.e. the individual׳s capacity to discriminate between lower and higher pain intensities and the response criterion, i.e. the subject׳s tendency to report pain during noxious stimulation due to psychological factors. [(11)C] raclopride binding potential (BP), defined as the ratio of specifically bound non-displaceable radioligand at equilibrium (BP(ND)) was used as measure of D2/D3 receptor availability. We found significant group effects of BP(ND) in striatal regions (left ventral striatum, left caudate nucleus and left nucleus accumbens) between FMS+ and FMS- compared to healthy subjects. Correlational analysis showed negative associations between TPT and D2/D3 receptor availability in the left caudate nucleus in FMS-, between TPT and D2/D3 receptor availability in the right caudate nucleus in FMS + and positive associations between TPT and D2/D3 receptor availability in the left putamen and right caudate nucleus in healthy controls. The response criterion was positively associated with D2/D3 receptor availability in the right nucleus accumbens in FMS - and negatively with D2/D3 receptor availability in the left caudate nucleus in healthy controls. Finally, no significant associations between D2/D3 receptor availability and discriminative capacity in any of the groups or regions were determined. These findings provide further support for a disruption of dopaminergic neurotransmission in FMS and implicate DA as important neurochemical moderator of differences in pain perception in FMS patients with and without co-morbid depression.

Arterial spin labeling imaging reveals widespread and Aβ-independent reductions in cerebral blood flow in elderly apolipoprotein epsilon-4 carriers

Changes in cerebral blood flow are an essential feature of Alzheimer’s disease and have been linked to apolipoprotein E-genotype and cerebral amyloid-deposition. These factors could be interdependent or influence cerebral blood flow via different mechanisms. We examined apolipoprotein E-genotype, amyloid beta-deposition, and cerebral blood flow in amnestic mild cognitive impairment using pseudo-continuous arterial spin labeling MRI in 27 cognitively normal elderly and 16 amnestic mild cognitive impairment participants. Subjects underwent Pittsburgh Compound B (PiB) positron emission tomography and apolipoprotein E-genotyping. Global cerebral blood flow was lower in apolipoprotein E ɛ4-allele carriers (apolipoprotein E4+) than in apolipoprotein E4− across all subjects (including cognitively normal participants) and within the group of cognitively normal elderly. Global cerebral blood flow was lower in subjects with mild cognitive impairment compared with cognitively normal. Subjects with elevated cerebral amyloid-deposition (PiB+) showed a trend for lower global cerebral blood flow. Apolipoprotein E-status exerted the strongest effect on global cerebral blood flow. Regional analysis indicated that local cerebral blood flow reductions were more widespread for the contrasts apolipoprotein E4+ versus apolipoprotein E4− compared with the contrasts PiB+ versus PiB− or mild cognitive impairment versus cognitively normal. These findings suggest that apolipoprotein E-genotype exerts its impact on cerebral blood flow at least partly independently from amyloid beta-deposition, suggesting that apolipoprotein E also contributes to cerebral blood flow changes outside the context of Alzheimer’s disease.

Multi atlas-based attenuation correction for brain FDG-PET imaging using a TOF-PET/MR scanner– comparison with clinical single atlas- and CT-based attenuation correction

In this work, we assessed the feasibility of attenuation correction (AC) based on a multi-atlas–based method (m-Atlas) by comparing it with a clinical AC method (single-atlas–based method [s-Atlas]), on a time-of-flight (TOF) PET/MRI scanner. Methods: We enrolled 15 patients. The median patient age was 59 y (age range, 31–80). All patients underwent clinically indicated whole-body 18F-FDG PET/CT for staging, restaging, or follow-up of malignant disease. All patients volunteered for an additional PET/MRI scan of the head (no additional tracer being injected). For each patient, 3 AC maps were generated. Both s-Atlas and m-Atlas AC maps were generated from the same patient-specific LAVA-Flex T1-weighted images being acquired by default on the PET/MRI scanner during the first 18 s of the PET scan. An s-Atlas AC map was extracted by the PET/MRI scanner, and an m-Atlas AC map was created using a Web service tool that automatically generates m-Atlas pseudo-CT images. For comparison, the AC map generated by PET/CT was registered and used as a gold standard. PET images were reconstructed from raw data on the TOF PET/MRI scanner using each AC map. All PET images were normalized to the SPM5 PET template, and 18F-FDG accumulation was quantified in 67 volumes of interest (VOIs; automated anatomic labeling atlas). Relative (%diff) and absolute differences (|%diff|) between images based on each atlas AC and CT-AC were calculated. 18F-FDG uptake in all VOIs and generalized merged VOIs were compared using the paired t test and Bland–Altman test. Results: The range of error on m-Atlas in all 1,005 VOIs was −4.99% to 4.09%. The |%diff| on the m-Atlas was improved by about 20% compared with s-Atlas (s-Atlas vs. m-Atlas: 1.49% ± 1.06% vs. 1.21% ± 0.89%, P < 0.01). In generalized VOIs, %diff on m-Atlas in the temporal lobe and cerebellum was significantly smaller (s-Atlas vs. m-Atlas: temporal lobe, 1.49% ± 1.37% vs. −0.37% ± 1.41%, P < 0.01; cerebellum, 1.55% ± 1.97% vs. −1.15% ± 1.72%, P < 0.01). Conclusion: The errors introduced using either s-Atlas or m-Atlas did not exceed 5% in any brain region investigated. When compared with the clinical s-Atlas, m-Atlas is more accurate, especially in regions close to the skull base.