PET/MR in Dementia and Other Neurodegenerative Diseases☆,☆☆
Introduction
Neurodegenerative diseases are characterized by a progressive and chronic loss of neural tissue in cognitive, motor, sensory, and other brain systems.1 As such, this entity of diseases covers the dementias; parkinsonian syndromes including movement diseases such as multisystem atrophies (MSA) type C and P, cortical-basal degeneration (CBD), and progressive supranuclear palsy (PSP); Huntington disease (HD); amyotrophic lateral sclerosis (ALS); and prion diseases like Creutzfeldt-Jakob disease (CJD). These diseases may share, at least in parts, a similar pattern of neuronal cell loss. However, the underlying cellular pathogens or neurotransmitter deficiencies are more disease-specific, ranging for instance from β-amyloid plaques (Alzheimer disease [AD] and some other dementias), hyperphosphorylated tau aggregates (AD, some other dementias, PSP, and CBD), or α-synuclein aggregates (Parkinson disease [PD] and Lewy body dementia) to cholinergic (AD, Lewy body dementia, and vascular dementia), dopaminergic (PD and some atypical parkinsonian syndromes), or γ-aminobutyric acid (HD) deficits.
In daily routine, most neurodegenerative diseases are diagnosed by a combination of clinical testing together with biomarkers, like brain imaging or cerebrospinal fluid analysis. In brain imaging of neurodegenerative disease, MRI represents the standard tool. This is based on the high spatial resolution and the high soft tissue contrast this modality offers as well as the rather specific findings in at least some movement disorders such as MSA and PSP. Often MRI is employed in suspected neurodegenerative diseases to exclude other nonneurodegenerative causes for the symptoms observed, like vascular disease, brain tumors, and traumatic or inflammatory brain changes. In addition, certain brain atrophy patterns may support the clinical diagnosis of distinct neurodegenerative diseases.
Brain PET has also been used over many years to diagnose neurodegenerative diseases. The main advantage of PET over MRI lies in its higher sensitivity to detect pathologies on a molecular level, which at least in principle permits more sensitive or even earlier diagnoses, because these diseases start with pathobiochemical processes that only lead to morphologic changes visible on MRI after a certain time period.
With the aim to take advantage of the merits of both imaging modalities, brain PET and MRI data acquired on separate imaging have been coregistered and subsequently analyzed for quite some time. With the recent emergence of integrated PET/MRI systems,2 this situation changed—combined PET/MRI now allows acquiring brain PET and MRI data simultaneously, promising not only improved image data quality and as such diagnostic performance but also improved convenience to patients with neurodegenerative diseases. Imaging a multitude of those disease-specific biomarkers is possible, which have already been proven valuable for differential diagnosis by comprehensive meta-analyses in the literature3 (Fig. 1).
This present overview aims at providing insight into the current knowledge and future potential of combined brain PET/MRI to simplify and improve diagnosis of neurodegenerative diseases in daily clinical routine.
Section snippets
Current PET Tracers to Image Neurodegenerative Diseases
The (patho)biochemical targets currently traced in clinical routine PET imaging of neurodegenerative diseases are summarized in Table 1. It is evident that [18F]FDG, which is transported into intracellular space by glucose 1 transporters followed by phosphorylation via the hexokinase reaction, is the most often employed PET tracer in this regard. [18F]FDG represents a universal marker of neuronal and synaptic integrity with relatively disease-specific uptake reduction patterns—in AD, for
Current MRI Techniques to Image Neurodegenerative Diseases
As noted previously, MRI is a standard imaging technique in the clinical routine diagnostic setup of many neurodegenerative diseases. Table 1 provides an overview on typical MR sequences that are employed to investigate different neurodegenerative diseases. By different examination protocols, MRI may reveal indicative temporal atrophy patterns according to established scores (Scheltens score) in AD, detect rather specific and exclusive mesencephalic atrophy (mickey mouse sign) in PSP, specific
Combined PET/MRI to Image Neurodegenerative Diseases
Taking the aforementioned status and advantages of both PET and MR to image neurodegenerative diseases, it was a logical early step to clinically test the potential of combined PET/MRI technology in improving and simplifying neurodegeneration imaging. Schlemmer et al were the first to show feasibility of simultaneous PET/MRI of the brain. Making use of a PET brain insert into a 3-T MR system, they successfully imaged brain glucose consumption by means of [18F]FDG simultaneously acquiring a
Future Potential of PET/MRI in Dementia Diseases
Summarizing the aforementioned and currently limited knowledge on useful applications of brain PET/MRI in neurodegenerative diseases, it becomes evident that developing the full potential of this new imaging technique still awaits its exploitation. For dementia imaging in particular, there are promising new PET tracers as well as MR sequence developments, which are provided in Table 2. For the PET component of the combined imaging tool, especially the new emergence of tau tracers and first
Future Potential of PET/MRI in Parkinsonian Syndromes
Regarding the application of combined PET/MRI in parkinsonian syndromes, the current clinical routine situation differs from that of dementias in so far as, like noted previously, nuclear imaging is mainly carried out by SPECT, and not by PET. However, novel PET tracers especially targeting DATs and α-synuclein are in development, which might change this situation in the future (Table 2), potentially opening the way for a wider use of PET and PET/MRI as first-line imaging in these
Future Potential of PET/MRI in Other Neurodegenerative Diseases
Unlike in dementias and parkinsonian syndromes, in the other neurodegenerative diseases discussed in this review such as HD, ALS, or prion diseases, no nuclear imaging techniques are used in current standard clinical routine. Here, MRI represents the standard imaging tool. Promising new developments regarding new PET tracers and novel MR sequences to improve imaging of the aforementioned diseases are given in Table 2. Some of the new emerging PET tracers target neuroinflammatory processes known
Summary and Conclusions
In summary, the recently established combined PET/MRI technology has a great but yet mostly unexplored potential to improve early and differential diagnosis of many neurodegenerative diseases. New emerging PET tracers, like tracers that bind to β-amyloid, tau, or α-synuclein aggregates, as well as new MR techniques, like DTI, rs-fMRI, or ASL, will broaden the diagnostic capabilities of combined PET/MRI. This may expand the current clinical routine strategy of measuring glucose utilization and
Acknowledgments
We would like to thank Martin Wehner, Solveig Tiepolt, Peter Werner, and Thies Jochimsen from the Leipzig University Department of Nuclear Medicine as well as Damian McLeod for their support in preparing this manuscript. The Leipzig University Department of Nuclear Medicine cyclotron, PET radiochemistry, and PET/MRI operating teams are greatly acknowledged for their diligence in acquiring and analyzing the brain PET/MRI data reported. We would also like to give our gratitude to Dominik Fritzsch
References (24)
- et al.
Reliability of semiquantitative 18F-FDG PET parameters derived from simultaneous brain PET/MRI: A feasibility study
Eur J Radiol
(2014) - et al.
The diagnosis of mild cognitive impairment due to Alzheimer׳s disease: Recommendations from the National Institute on Aging-Alzheimer׳s Association workgroups on diagnostic guidelines for Alzheimer׳s disease
Alzheimers Dement
(2011) - et al.
The diagnosis of dementia due to Alzheimer׳s disease: Recommendations from the National Institute on Aging-Alzheimer׳s Association workgroups on diagnostic guidelines for Alzheimer׳s disease
Alzheimers Dement
(2011) - et al.
Meta-analysis based SVM classification enables accurate detection of Alzheimer׳s disease across different clinical centers using FDG-PET and MRI
Psychiatry Res
(2013) Molecular basis of the neurodegenerative disorders
N Engl J Med
(1999)- et al.
Simultaneous PET-MRI: A new approach for functional and morphological imaging
Nat Med
(2008) - et al.
Combined imaging markers dissociate Alzheimer׳s disease and frontotemporal lobar degeneration—An ALE meta-analysis
Front Aging Neurosci
(2011) - et al.
Appropriate use criteria for amyloid PET: A report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer׳s Association
J Nucl Med
(2013) - et al.
Simultaneous MR/PET imaging of the human brain: Feasibility study
Radiology
(2008) - et al.
Clinical applications of hybrid PET/MRI in neuroimaging
Clin Nucl Med
(2013)
Systematic comparison of the performance of integrated whole-body PET/MR imaging to conventional PET/CT for 18F-FDG brain imaging in patients examined for suspected dementia
J Nucl Med
Segmentation-based MR attenuation correction including bones also affects quantitation in brain study: An initial result of 18F-FP-CIT PET/MR for patients with parkinsonism
J Nucl Med
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All the authors contributed equally.
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The acquisition of the Leipzig University combined PET/MR system was funded by the German Research Foundation through Grant no. SA 669/9-1.
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H.B. and O.S. received speaker and consultant honoraria from Siemens Healthcare (Erlangen, Germany) related to combined PET/MRI and from Piramal Imaging (Berlin, Germany) related to amyloid PET imaging. O.S. and M.L.S. were supported by LIFE—Leipzig Research Center for Civilization Diseases at the University of Leipzig—funded by the European Union, European Regional Development Fund, and by the Free State of Saxony within the framework of the excellence initiative, by the German Consortium for Frontotemporal Lobar Degeneration, by the German Federal Ministry of Education and Research (M.L.S.), and by the Parkinson Disease Foundation (M.L.S.; Grant No. PDF-IRG-1307). K.T.H. received speaker honoraria from Bayer Healthcare and Bracco related to MRI.