Direct comparison of fluorodeoxyglucose positron emission tomography and arterial spin labeling magnetic resonance imaging in Alzheimer’s disease

Direct comparison of fluorodeoxyglucose positron emission tomography and arterial spin labeling magnetic resonance imaging in Alzheimer’s disease - pdf for free download
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Category: Magnetic Resonance Imaging, Positron Emission Tomography, Brain Mapping, Humans, PET imaging, Female, Male, Clinical Sciences, Aged, Middle Aged, Cerebral Blood Flow, Alzheimer Disease, ASL (Arterial Spin Labeling), Neurosciences, Case Control Studies, Magnetic resonance image, Female, Male, Clinical Sciences, Aged, Middle Aged, Cerebral Blood Flow, Alzheimer Disease, ASL (Arterial Spin Labeling), Neurosciences, Case Control Studies, Magnetic resonance image

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NIH Public Access Author Manuscript Alzheimers Dement. Author manuscript; available in PMC 2013 January 01.

NIH-PA Author Manuscript

Published in final edited form as: Alzheimers Dement. 2012 January ; 8(1): 51–59. doi:10.1016/j.jalz.2011.06.003.

Direct Comparison of FDG-PET and ASL-MRI in Alzheimer’s Disease Erik S. Musiek1, Yufen Chen2, Marc Korczykowski2, Babak Saboury3, Patricia M. Martinez4, Janet S. Reddin3, Abass Alavi3, Daniel Y. Kimberg2, David A. Wolk1, Per Julin5, Andrew B. Newberg3, Steven E. Arnold4, and John A. Detre1,2,3 1Department of Neurology, University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104 2Center

for Functional Neuroimaging, University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104 3Department

of Radiology, University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104

4Department

of Psychiatry, University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104

NIH-PA Author Manuscript

5AstraZeneca

R&D, Västra Mälarehamnen 9, Södertälje, Sweden, SE-151 85

Abstract BACKGROUND—The utility flourodeoxyglucose PET (FDG-PET) imaging in Alzheimer’s Disease (AD) diagnosis is well established. Recently, measurement of cerebral blood flow using arterial spin labeling MRI (ASL-MRI) has shown diagnostic potential in AD, though it has never been directly compared to FDG-PET. METHODS—We employed a novel imaging protocol to obtain FDG-PET and ASL-MRI images concurrently in 17 AD patients and 19 age-matched controls. Paired FDG-PET and ASL-MRI images from 19 controls and 15 AD patients were included for qualitative analysis, while paired images 18 controls and 13 AD patients were suitable for quantitative analyses.

NIH-PA Author Manuscript

RESULTS—The combined imaging protocol was well tolerated. Both modalities revealed very similar regional abnormalities in AD, as well as comparable sensitivity and specificity for the detection of AD following visual review by two expert readers. Interobserver agreement was better for FDG-PET (kappa 0.75, SE 0.12) than ASL-MRI (kappa 0.51, SE 0.15), intermodality agreement was moderate to strong (kappa 0.45-0.61), and readers were more confident of FDGPET reads. Simple quantitative analysis of global cerebral FDG uptake (FDG-PET) or whole brain cerebral blood flow (ASL-MRI) showed excellent diagnostic accuracy for both modalities, with area under ROC curves of 0.90 for FDG-PET (95% CI 0.79-0.99) and 0.91 for ASL-MRI (95% CI 0.80-1.00). CONCLUSIONS—Our results demonstrate that FDG-PET and ASL-MRI identify similar regional abnormalities and have comparable diagnostic accuracy in a small population of AD patients, and support the further study of ASL-MRI in dementia diagnosis.

© 2011 Elsevier Inc. All rights reserved. Corresponding Author: Dr. John Detre, Center for Functional Neuroimaging, Univ. of Pennsylvania, 3 Gates, 3400 Spruce St., Philadelphia, PA, 19104. [email protected] Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The other authors report no conflicts of interest and have nothing to disclose.

Musiek et al.

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Keywords

NIH-PA Author Manuscript

ASL; FDG; PET; MRI; Alzheimer’s disease; spin label; fluorodeoxyglucose; dementia

1. INTRODUCTION Considerable effort over the past 20 years has been targeted at the improved diagnosis of Alzheimer Disease (AD). Regional hypometabolism on positron emission tomographic imaging with [18F]-fluorodeoxyglucose (FDG-PET) has been well established as a marker of AD (1-4). However, enthusiasm for FDG-PET in AD diagnosis and monitoring has been mitigated by limited availability, radiation exposure, and expense.

NIH-PA Author Manuscript

Arterial spin labeling perfusion MRI (ASL-MRI) uses magnetically labeled arterial blood water as a tracer (5), and has emerged as a noninvasive and reliable modality for quantitative measurement of regional cerebral blood flow (CBF) (6). Since regional CBF and glucose metabolism are generally tightly coupled (7), regional ASL-MRI measures of CBF are expected to closely parallel metabolic changes seen with FDG-PET. Indeed, several groups have demonstrated that ASL-MRI can differentiate AD or mild cognitive impairment patients from controls (8-14). ASL-MRI can be performed alongside structural MRI sequences during the routine dementia workup and requires no exogenous contrast or radiation exposure. Thus, ASL represents a potentially appealing functional imaging modality for AD diagnosis and monitoring. To date, however, no studies have directly compared ASL-MRI to FDG-PET in AD patients. Herein, we compare FDG-PET and ASLMRI imaging in a cohort of AD patients and controls. To eliminate physiological variability between FDG-PET and ASL-MRI scans, we employed a novel methodological approach in which FDG is administered during the acquisition of ASL-MRI (15), providing concurrent measurements of regional CBF and metabolism.

2. METHODS 2.1. Subjects

NIH-PA Author Manuscript

17 subjects with clinically-diagnosed AD and 19 cognitively normal controls were recruited from the cohort of the Penn Memory Center/ Alzheimer’s Disease Center. Ultimately, paired ASL-MRI and FDG-PET images from all 19 controls and 15 AD patients were included for qualitative analysis (expert reader diagnosis, sensitivity, specificity, kappa, and ischemic burden analyses), and paired images from 18 controls and 13 AD patients were included for quantitative analyses (FDG SUV ratio, ASL CBF, ROC curve analysis). Control and AD patients were matched for age and years of education (Table 1). All patients underwent full neurocognitive assessment, including all elements of the National Alzheimer’s Coordinating Center’s Uniform Data Set that is conducted by all National Institute of Aging-sponsored Alzheimer Disease Centers (16). All controls had a Clinical Dementia Rating (CDR) of 0 and a mini mental status score (MMSE) > 27, and all clinically diagnosed AD patients included in the study had a CDR of 0.5 or more, and an MMSE less than 25 (Table 1). The mean CDR for AD patients was 1.04±0.72. Exclusion criteria included age <50 or >80, history of stroke or other known intracranial abnormality, clinically relevant abnormalities on routine bloodwork including glucose > 200, contraindication to MRI or PET, and history of Axis I psychiatric disease or substance abuse. All scans were performed between December 2008 and November 2009, and current MMSE testing was performed on all patients during that interval.

Alzheimers Dement. Author manuscript; available in PMC 2013 January 01.

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2.2. Imaging Protocol

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In order to most closely correlate ASL-MRI findings with FDG-PET, a unique imaging protocol was employed. At the initiation on the ASL-MRI scan, while in the scanner, 5mCi of FDG was injected via intravenous catheter, such that FDG uptake and ASL imaging occurred simultaneously. PET imaging was then performed 40 minutes later. 2.3. MRI Imaging 3T high resolution T1-weighted images were acquired using MPRAGE (17). ASL images were acquired with pseudo-continuous labeling (mean Gz=0.6mT/m, 1640 Hanning window-shaped radiofrequency (RF) pulses for a total labeling duration =1.8s, RF duration=500μs, RF gap=360μs, postlabeling delay=1.5s) and gradient-echo echo-planar imaging . Imaging parameters for ASL include TE/TR=17ms/4s, image resolution=3.4×3.4×6mm3, 18 axial slices with 1mm gap prescribed to cover the entire brain. An ascending acquisition order was used, and ramp sampling was used employed with a readout bandwidth was 3004Hz/voxel. All 18 slices were acquired during the same acquisition sesion. Each ASL scan consisted of 59 pairs of interleaved control and tag images, and three ASL scans were concatenated to improve signal-to-noise ratio.

NIH-PA Author Manuscript

ASL and structural images were coregistered using SPM5 (The Wellcome Department of Imaging Neuroscience, London, UK). Pairwise subtraction images were generated and averaged using in-house developed Matlab (The Mathworks Inc., Natick, MA, USA) script. These were converted to quantitative CBF maps in units of ml/100g/min based on a single compartment ASL model (18), then spatially normalized to Montreal Neurological Institute (MNI) space with 2mm isotropic resolution and smoothed with an isotropic kernel of 8mm to facilitate comparison with the similarly normalized PET images. CBF measurements represent whole-brain CBF values with no partial volume correction or grey matter coregistration. 2.4. FDG-PET Imaging PET imaging was carried out based on the ADNI PET imaging protocol (19). At the initiation of the ASL scan, patients were injected with FDG. PET imaging was initiated 40 minutes after the administration of FDG, and was conducted in a darkened, quiet room. Images were obtained on an Allegro scanner (Philips). Images were reconstructed in the transaxial plane using iterative reconstruction and 137Cesium transmission scan for attenuation correction.

NIH-PA Author Manuscript

The whole brain standardized uptake value ratio was determined by defining an automated volume of interest encompassing the entire brain parenchyma with an intensity >25% of the maximal voxel intensity. The mean SUV for the whole brain was determined automatically, and divided by the mean SUV of a volume of interest encompassing one cerebellar hemisphere. 2.5. Qualitative Analysis Each ASL-MRI and FDG-PET image was independently reviewed in a blinded manner by two expert nuclear medicine physicians with >10 years experience reading functional brain images...

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