Using visual scales to determine brain atrophy subtypes in Alzheimer’s Disease

AD subtypes based on patterns of brain atrophy. Regional atrophy was measured with the MTA, PA, and GCA-F visual rating scales based only on T1-weighted images. In the 3 visual rating scales, a score of zero denotes no atrophy, whereas scores from 1 to 3 (PA and GCA-F) or 4 (MTA) indicate an increasing degree of atrophy. The typical AD subtype was defined as abnormal MTA together with abnormal PA and/or abnormal GCA-F. The limbic-predominant subtype was defined as abnormal MTA alone with normal PA and GCA-F. The hippocampal-sparing subtype included abnormal PA and/or abnormal GCA-F but normal MTA. The minimal atrophy subtype was defined as normal scores in MTA, PA, and GCA-F. The figure shows examples of each subtype in axial and coronal sections of the brain. AD, Alzheimer’s disease; MTA, medial temporal atrophy scale; PA, posterior atrophy scale; GCA-F, global cortical atrophy scale – frontal subscale; A, anterior part of the brain; P, posterior part of the brain; R, right; L, left.

Medial temporal atrophy in preclinical dementia: visual and automated assessment during six year follow-up

Medial temporal lobe (MTL) atrophy is an important morphological marker of many dementias and is closely related to cognitive decline. In this study we aimed to characterize longitudinal progression of MTL atrophy in 93 individuals with subjective cognitive decline and mild cognitive impairment followed up over six years, and to assess if clinical rating scales are able to detect these changes. All MRI images were visually rated according to Scheltens' scale of medial temporal atrophy (MTA) by two neuroradiologists and AVRA, a software for automated MTA ratings. The images were also segmented using FreeSurfer's longitudinal pipeline in order to compare the MTA ratings to volumes of the hippocampi and inferior lateral ventricles. We found that MTL atrophy rates increased with CSF biomarker abnormality, used to define preclinical stages of Alzheimer's Disease. Both AVRA's and the radiologists' MTA ratings showed a similar longitudinal trajectory as the subcortical volumes, suggesting that visual rating scales provide a valid alternative to automatic segmentations. While the MTA scores from each radiologist showed strong correlations to subcortical volumes, the inter-rater agreement was low. We conclude that the main limitation of quantifying MTL atrophy with visual ratings in clinics is the subjectiveness of the assessment.

Imaging Patterns of Toxic and Metabolic Brain Disorders

Illustration shows the most important general imaging patterns in toxic and metabolic brain disorders. White areas = areas of involvement. These include symmetric basal ganglia and/or thalami involvement (axial view) (A); symmetric dentate nuclei involvement (axial view) (B); prominent cortical gray matter involvement (axial view) (C); symmetric periventricular white matter involvement (with gray matter sparing) (axial view) (D); corticospinal tract involvement (axial view) (E); corpus callosum involvement (coronal view) (F); asymmetric white matter involvement (demyelinating disease pattern) (axial view) (G); parieto-occipital subcortical vasogenic edema (axial view) (H); and central pons involvement (axial view) (I).

Linear vs volume measures of ventricle size in hydrocephalus: relation to present and future gait and cognition

Objective To compare the clinical utility of volume-based ratios with the standard linear ratio of Evans index (EI) by examining their associations with gait, cognition, and other patient and imaging variables. 
 Methods From MRI scans of 1,774 participants in the Mayo Clinic Study of Aging, we calculated 3 ventricle size measures: Evan index (frontal horn width divided by widest width of skull inner table), total ventricular volume, and frontal horn volume as ratios of total intracranial volume. Gait was measured by a timed 25-foot walk and cognition by a composite of psychometric tests. We also evaluated variables associated with the measures of ventricular size. Further, we evaluated gait and cognition associations with MRI of extraventricular findings seen in normal-pressure hydrocephalus: disproportionate enlargement of subarachnoid space (DESH) and focal sulcal dilations (FSD). 
 Results Ventricular volume measures had stronger association with gait and cognition measures than EI. In decreasing order of strength of association with ventricle size were DESH, FSD, white matter hyperintensity volume ratio, age, male sex, cortical thickness, and education. Modest evidence was observed that FSD was associated with future decline in gait and cognition. 
 Conclusion Ventricular volume measures are clinically more useful than EI in indicating current and future gait and cognition. Multiple factors are associated with ventricle volume size, including FSD and DESH, suggesting that changes in CSF dynamics may go beyond simple ventriculomegaly. 


Thalamic nuclei in frontotemporal dementia: Mediodorsal nucleus involvement is universal but pulvinar atrophy is unique to C9orf72

Thalamic atrophy is a common feature across all forms of FTD but little is known about specific nuclei involvement. We aimed to investigate in vivo atrophy of the thalamic nuclei across the FTD spectrum. A cohort of 402 FTD patients (age: mean(SD) 64.3(8.2) years; disease duration: 4.8(2.8) years) was compared with 104 age‐matched controls (age: 62.5(10.4) years), using an automated segmentation of T1‐weighted MRIs to extract volumes of 14 thalamic nuclei. Stratification was performed by clinical diagnosis (180 behavioural variant FTD (bvFTD), 85 semantic variant primary progressive aphasia (svPPA), 114 nonfluent variant PPA (nfvPPA), 15 PPA not otherwise specified (PPA‐NOS), and 8 with associated motor neurone disease (FTD‐MND), genetic diagnosis (27 MAPT, 28 C9orf72, 18 GRN), and pathological confirmation (37 tauopathy, 38 TDP‐43opathy, 4 FUSopathy). The mediodorsal nucleus (MD) was the only nucleus affected in all FTD subgroups (16–33% smaller than controls). The laterodorsal nucleus was also particularly affected in genetic cases (28–38%), TDP‐43 type A (47%), tau‐CBD (44%), and FTD‐MND (53%). The pulvinar was affected only in the C9orf72 group (16%). Both the lateral and medial geniculate nuclei were also affected in the genetic cases (10–20%), particularly the LGN in C9orf72 expansion carriers. Use of individual thalamic nuclei volumes provided higher accuracy in discriminating between FTD groups than the whole thalamic volume. The MD is the only structure affected across all FTD groups. Differential involvement of the thalamic nuclei among FTD forms is seen, with a unique pattern of atrophy in the pulvinar in C9orf72 expansion carriers.

Brain volumes and their ratios in Alzheimer´s disease on magnetic resonance imaging segmented using Freesurfer 6.0

  • Study shows 44 brain regions volume changes with Alzheimer's disease. 
  • Volumes were calculated both in absolute values and ratios to the whole brain volume. 
  • The hippocampo-horn proportion is effective for hippocampal atrophy evaluation. 
  • This method can be simplified for visual assessment.

A new MR imaging index for differentiation of progressive supranuclear palsy-parkinsonism from Parkinson's disease


  • Distinguishing PSP-P from PD is challenging in the early stages of the disease.
  • Few data exist on the usefulness of MRPI for diagnosing PSP-P patients.
  • MRPI 2.0 is a new version of MRPI which includes the 3rd ventricular width.
  • MRPI 2.0 accurately differentiated patients with PSP-P from those with PD.
  • MRPI 2.0 accurately diagnosed PSP-P in the absence of vertical ocular palsy.



Differentiating clinically progressive supranuclear palsy-parkinsonism (PSP-P) from Parkinson's disease (PD) may be challenging, especially in the absence of vertical supranuclear gaze palsy (VSGP). The Magnetic Resonance Parkinsonism Index (MRPI) has been reported to accurately distinguish between PSP and PD, yet few data exist on the usefulness of this biomarker for the differentiation of PSP-P from PD.


Thirty-four patients with PSP-P, 46 with PSP-Richardson's syndrome (PSP-RS), 53 with PD, and 53 controls were enrolled. New consensus criteria for the clinical diagnosis of PSP were used as the reference standard. The MRPI, and a new index termed MRPI 2.0 including the measurement of the third ventricle width (MRPI multiplied by third ventricle width/frontal horns width ratio), were calculated on T1-weighted MR images.


The MRPI differentiated patients with PSP-P from those with PD with sensitivity and specificity of 73.5% and 98.1%, respectively, while the MRPI 2.0 showed higher sensitivity (100%) and similar specificity (94.3%) in differentiating between these two groups. Both biomarkers showed excellent performance in differentiating PSP-P patients with VSGP from those with PD, but the MRPI 2.0 was much more accurate (95.8%) than MRPI in differentiating PSP-P patients with slowness of vertical saccades from PD patients.


The MRPI 2.0 accurately differentiated PSP-P patients from those with PD. This new index was more powerful than MRPI in differentiating PSP patients in the early stage of the disease with slowness of vertical saccades from patients with PD, thus helping clinicians to consolidate the diagnosis based on clinical features, in vivo.