Quantitative Structural MRI for Neurocognitive Disorders

Cyrus A. Raji, MD, PhD
Department of Neurology
Washington University, St. Louis

Somayeh Meysami, MD
Department of Neurology
David Geffen School of Medicine at UCLA
Los Angeles, CA

Mario F. Mendez, MD, PhD
Department of Neurology
David Geffen School of Medicine at UCLA
Los Angeles, CA

Source

Practical Neurology
practicalneurology.com

Introduction

Neurocognitive disorders are prevalent clinical problems. Among the most common are Alzheimer disease (AD) dementia and frontotemporal dementia (FTD), respectively the first and second most common neurodegenerative causes of dementia worldwide. Collectively, these conditions affect almost 6 million persons in the US alone.¹,² Traumatic brain injury (TBI) is also a common problem affecting 2.5 million persons annually.³ TBI increases the risk for later dementia and chronic traumatic encephalopathy (CTE).⁴ Because all of these disorders can present with cognitive impairment, the ability to apply improved diagnostic tools is crucial for patient care.

The current clinical standard of care in neuroradiology involves visual inspection of brain MRI. When attempting to detect the earliest volume loss related to brain atrophy, however, visual inspection alone lacks sensitivity compared with automated methods.⁵ The purpose of this review is to present a brief outline of available quantitative analytic methods that can be applied to brain MRI to detect volume loss from atrophy in AD dementia; behavioral variant FTD (bvFTD), which is the most common form of FTD; and TBI.

Although there are other imaging methods for the evaluation of neurocognitive disorders, there are several reasons to emphasize the volumetric quantification of brain MRI. First, patient access is maximized compared with neuronuclear methods such as positron emission tomography (PET). Second, the cost of an MRI is 60% lower than glucose metabolic imaging with fluorodeoxyglucose PET (FDG-PET) and 80% reduced in cost compared to an amyloid PET scan.⁶ Third, quantification of hippocampal volume loss on MRI is recognized as a key metric of neurodegeneration in the amyloid, tau, and neurodegeneration (ATN) framework.⁷ It is also possible that developing blood-based biomarkers for amyloid and tau may obviate the clinical use of amyloid or tau PET imaging in the future. (See Blood Tests for Alzheimer Disease in this issue).⁸

Findings in AD

AD dementia is a progressive disorder leading to cognitive decline in multiple domains including episodic memory, language, and visuospatial skills.⁹ Volumetric quantification of brain MRI in AD dementia most commonly includes the temporal and parietal lobes as well as the hippocampus.¹⁰

The magnitude of this change varies with the type of FDA-cleared software used for analysis—a 5th percentile and lower cutoff to distinguish normal from abnormal with 1 software package (NeuroQuant) and a 25th percentile or lower for the other available software package (NeuroReader).¹¹,¹² Whereas NeuroQuant relies on multiple normal databases drawn from a combination of research databases and clinical samples with an age range of 3 to 100 years,¹³ the Neuroreader database is drawn currently from Alzheimer’s Disease Neuroimaging Initiative (ADNI) with an age range of 60 to 90 years.

Ventricular enlargement from volume loss is also a feature of AD and manifests typically as volumes of more than the 75th percentile of normal. A separate FDA-cleared software program, Icometrix, has recently shown high diagnostic performance when compared with the research program, Freesurfer.¹³ An additional program (Quantib), also cleared by the FDA, uses normative data from the population-based Rotterdam Study.¹⁴

Hippocampal volume loss alone is not entirely specific for AD and can be observed in other disorders, including mesial temporal sclerosis¹⁵ and hippocampal sclerosis.¹⁶ Quantification of specific hippocampal subfields may bridge diagnostic gaps but is not currently available in FDA-cleared software.¹⁷

Findings in BvFTD

The misdiagnosis of bvFTD is common, with up to 60% of persons diagnosed with bvFTD by community specialists having other conditions on further evaluation by specialists.¹⁸ Volumetric quantification findings are distributed in the frontal and temporal lobes, and a meta-analysis demonstrates affected regions including anterior medial frontal cortex, anterior cingulate gyrus, thalamus, and anterior insula.¹⁹ Progressive posterior frontal lobe atrophy occurs with disease progression.²⁰

Findings in TBI

Using NeuroQuant software, atrophy was found in 50% of cases of mostly mild TBI, whereas visual radiologic interpretations detected atrophy in only 10%.²¹ Longitudinal studies showed abnormal asymmetry in 83.3% and progressive atrophy in 70% of cases, while visual interpretation detected none.²²

Neuroreader measures additional brainstem structures implicated in TBI and chronic traumatic encephalopathy.²³ Longitudinal case reports demonstrated progressive midbrain and ventral diencephalon atrophy in a former football player.²⁴ In a larger cohort, ventral diencephalon was the most atrophic region, whereas the hippocampus was least affected.²⁵

Conclusions

Volumetric MR quantification improves detection of brain atrophy across neurodegenerative disease and traumatic brain injury and is readily available for clinical use. Proper ordering of a 3D T1 protocol and close collaboration between neurologists and neuroradiologists are essential for meaningful interpretation and patient care integration.

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