Using simultaneous PET/MRI to compare the accuracy of diagnosing frontotemporal dementia by arterial spin labelling MRI and FDG-PET

Abstract

Purpose: The clinical utility of FDG-PET in diagnosing frontotemporal dementia (FTD) has been well demonstrated over the past decades. On the contrary, the diagnostic value of arterial spin labelling (ASL) MRI - a relatively new technique - in clinical diagnosis of FTD has yet to be confirmed. Using simultaneous PET/MRI, we evaluated the diagnostic performance of ASL in identifying pathological abnormalities in FTD (FTD) to determine whether ASL can provide similar diagnostic value as FDG-PET.

Methods: ASL and FDG-PET images were compared in 10 patients with FTD and 10 healthy older adults. Qualitative and quantitative measures of diagnostic equivalency were used to determine the diagnostic utility of ASL compared to FDG-PET. Sensitivity, specificity, and inter-rater reliability were calculated for each modality from scores of subjective visual ratings and from analysis of regional mean values in thirteen a priori regions of interest (ROI). To determine the extent of concordance between modalities in each patient, individual statistical maps generated from comparison of each patient to controls were compared between modalities using the Jaccard similarity index (JI).

Results: Visual assessments revealed lower sensitivity, specificity and inter-rater reliability for ASL (66.67%/62.12%/0.2) compared to FDG-PET (88.43%/90.91%/0.61). Across all regions, ASL performed lower than FDG-PET in discriminating patients from controls (areas under the receiver operating curve: ASL = 0.75 and FDG-PET = 0.87). In all patients, ASL identified patterns of reduced perfusion consistent with FTD, but areas of hypometabolism exceeded hypoperfused areas (group-mean JI = 0.30 ± 0.22).

Conclusion: This pilot study demonstrated that ASL can detect similar spatial patterns of abnormalities in individual FTD patients compared to FDG-PET, but its sensitivity and specificity for discriminant diagnosis of a patient from healthy individuals remained unmatched to FDG-PET. Further studies at the individual level are required to confirm the clinical role of ASL in FTD management.

Keywords: Arterial spin labelling MRI; FDG-PET; Frontotemporal dementia; Hybrid PET/MRI.

Fig. 1

A priori regions of interest (ROIs) masks overlaid on a single subject T1 image. ROIs comprised of frontal sub-regions (1–4), insula (5), anterior cingulate (6), precuneus (7), caudate (8) and temporal sub-regions (9–13) bilaterally.

Fig. 2

Patient #2, rCMRglc (A) and rCBF (B) maps, illustrating images reviewed by readers. Slices in coronal, sagittal and axial are shown to highlight the potential of both modalities to yield similar diagnosis. All readers chose bvFTD diagnosis after reviewing either A or B images. (C) t-maps of voxelwise differences between patient and control group indicate areas of lower CBF (red-yellow) and less FDG uptake (blue-green). A large area overlapping hypometabolic and hypoperfusion regions can be seen in (D; green) with measured Jaccard index of 0.41. Restricting the concordance to a priori ROIs (purple) improved the Jaccard index to 0.60. Images are displayed in radiological convention.

Fig. 3

A comparison of measures of diagnostic performance between ASL-CBF and FDG-PET from visual assessments. Significant difference between modalities are indicated by * (p < 0.05). Error bars correspond to standard deviation. NPV and PPV are the negative and positive predictive value.

Fig. 4

Regional grouped means of glucose uptake (top) and cerebral blood flow (bottom). Errors bars indicate standard deviation. Significant difference between groups was seen in all regions except † where p > 0.05. CTL = control subjects, PT = FTD patients.

Fig. 5

Association between ASL-CBF and FDG-PET across all regions of interests. A strong correlation between modalities can be seen in regression plot (p < 0.001) (left) and the Bland-Altman plot (right) reveals close agreement between modalities with slight systematic bias possibly due to relatively poor SNR of the ASL signal (− 0.14 to 0.29, r = 0.07, p = 0.01). HC = control subjects.

Fig. 6

Comparison between cerebral perfusion and glucose metabolism in key regions across both groups. Moderate-to-strong correlation between perfusion and metabolism can be seen in all regions (top panel), and significant differences (p < 0.05) between patients and controls (bottom panel) were found in all regions for FDG-PET and in the frontal lobe and anterior cingulate for ASL-CBF. Line plots of mean, and 95% confidence intervals for the mean are included in dot plots.