Hannu J. Aronen

The significance of medial temporal lobe atrophy A postmortem MRI study in the very old

Background: Medial temporal lobe atrophy (MTA) is a sensitive radiologic marker for Alzheimer disease (AD) and associated with cognitive impairment. The value of MTA in the oldest old (>85 years old) is largely unknown. Methods: A total of 132 formalin-fixed brains from the Vantaa 85+ community-based study were subjected to postmortem MRI. Visual ratings of MTA were determined in a blinded fashion and compared with neuropathologic findings and clinical assessment (dementia according to Diagnostic and Statistical Manual of Mental Disorders-III-R). Results: A strong relationship was found between MTA scores and Alzheimer pathology (p < 0.001). The previously proposed cutoff MTA score >2 correctly excluded subjects with no or borderline Alzheimer-type pathology (45/48), but was not very sensitive for AD (modified National Institute on Aging-Reagan Institute criteria). MTA scores >2 were also found in subjects with other primary neurodegenerative hippocampal pathology including hippocampal sclerosis, Lewy-related pathology, and argyrophilic grain disease, either alone or in combination with Alzheimer-type pathology. High MTA scores were associated with clinical dementia—in this subgroup, sensitivity was 63% and specificity 69% for AD. Conclusion: Medial temporal lobe atrophy (MTA) on postmortem MRI is sensitive to primary degenerative hippocampal pathology in the very old, but not specific for Alzheimer-type pathology. MTA scores of 2 or less are not frequently associated with dementia. GLOSSARY: AD = Alzheimer disease; AgD = argyrophilic grain disease; CERAD = Consortium to Establish a Registry for Alzheimer’s Disease; DLB = dementia with Lewy bodies; HS = hippocampal sclerosis; L-rP = Lewy-related pathology; MCI = mild cognitive impairment; MTA = medial temporal lobe atrophy.

Frontal lobe white matter hyperintensities and neurofibrillary pathology in the oldest old

Background: Current studies suggest an interaction between vascular mechanisms and neurodegenerative processes that leads to late-onset Alzheimer disease (AD). We tested whether AD pathology was associated with white matter hyperintensities (WMH) or cerebral infarcts in the oldest old individuals. Methods: Brains from 132 subjects over 85 years old, who came to autopsy from the Vantaa 85+ population-based cohort, were scanned by postmortem MRI and examined for neuropathologic changes. Coronal images were analyzed to determine the degree of frontal and parietal periventricular WMH (PVWMH) and deep WMH (DWMH) and cerebral infarcts. Neuropathologic variables included Consortium to Establish a Registry for Alzheimers Disease scores for neuritic plaques and Braak staging among subjects in 5 groups: normal aging (NA), borderline with insufficient AD pathology, AD, AD plus other pathology, and other primary degenerative diseases. Results: Frontal DWMH were detected in >50% of the sample. Both frontal PVWMH and DWMH were significantly more extensive in the AD group compared to the NA group or the NA and borderline groups combined. Frontal PVWMH and DWMH were also associated with increased Braak staging (p = 0.03) and the neuritic plaque load (p = 0.01). Further analysis revealed there were a greater number of cerebral infarcts associated with frontal DWMH (p = 0.03) but not with frontal PVWMH. Conclusions: Our study showed an association between neurofibrillary pathology and frontal PVWMH and DWMH (rather than parietal), as a surrogate of small vessel disease, particularly in very old community-dwelling individuals.

Abnormal hippocampal shape in offenders with psychopathy

Posterior hippocampal volumes correlate negatively with the severity of psychopathy, but local morphological features are unknown. The aim of this study was to investigate hippocampal morphology in habitually violent offenders having psychopathy. Manual tracings of hippocampi from magnetic resonance images of 26 offenders (age: 32.5 ± 8.4), with different degrees of psychopathy (12 high, 14 medium psychopathy based on the Psychopathy Checklist Revised), and 25 healthy controls (age: 34.6 ± 10.8) were used for statistical modelling of local changes with a surface‐based radial distance mapping method. Both offenders and controls had similar hippocampal volume and asymmetry ratios. Local analysis showed that the high psychopathy group had a significant depression along the longitudinal hippocampal axis, on both the dorsal and ventral aspects, when compared with the healthy controls and the medium psychopathy group. The opposite comparison revealed abnormal enlargement of the lateral borders in both the right and left hippocampi of both high and medium psychopathy groups versus controls, throughout CA1, CA2‐3 and the subicular regions. These enlargement and reduction effects survived statistical correction for multiple comparisons in the main contrast (26 offenders vs. 25 controls) and in most subgroup comparisons. A statistical check excluded a possible confounding effect from amphetamine and polysubstance abuse. These results indicate that habitually violent offenders exhibit a specific abnormal hippocampal morphology, in the absence of total gray matter volume changes, that may relate to different autonomic modulation and abnormal fear‐conditioning. Hum Brain Mapp, 2010.

Prospective evaluation of planar bone scintigraphy, SPECT, SPECT/CT, 18F-NaF PET/CT and whole body 1.5T MRI, including DWI, for the detection of bone metastases in high risk breast and prostate cancer patients: SKELETA clinical trial

Purpose. Detection of bone metastases in breast and prostate cancer patients remains a major clinical challenge. The aim of the current trial was to compare the diagnostic accuracy of 99mTc-hydroxymethane diphosphonate (99mTc-HDP) planar bone scintigraphy (BS), 99mTc-HDP SPECT, 99mTc-HDP SPECT/CT, 18F-NaF PET/CT and whole body 1.5 Tesla magnetic resonance imaging (MRI), including diffusion weighted imaging, (wbMRI+DWI) for the detection of bone metastases in high risk breast and prostate cancer patients. Material and methods. Twenty-six breast and 27 prostate cancer patients at high risk of bone metastases underwent 99mTc-HDP BS, 99mTc-HDP SPECT, 99mTc-HDP SPECT/CT, 18F-NaF PET/CT and wbMRI+DWI. Five independent reviewers interpreted each individual modality without the knowledge of other imaging findings. The final metastatic status was based on the consensus reading, clinical and imaging follow-up (minimal and maximal follow-up time was 6, and 32 months, respectively). The bone findings were compared on patient-, region-, and lesion-level. Results. 99mTc-HDP BS was false negative in four patients. In the region-based analysis, sensitivity values for 99mTc-HDP BS, 99mTc-HDP SPECT, 99mTc-HDP SPECT/CT, 18F-NaF PET/CT, and wbMRI+DWI were 62%, 74%, 85%, 93%, and 91%, respectively. The number of equivocal findings for 99mTc-HDP BS, 99mTc-HDP SPECT, 99mTc-HDP SPECT/CT, 18F-NaF PET/CT and wbMRI+DWI was 50, 44, 5, 6, and 4, respectively. Conclusion. wbMRI+DWI showed similar diagnostic accuracy to 18F-NaF PET/CT and outperformed 99mTc-HDP SPECT/CT, and 99mTc-HDP BS.

Functional imaging of localized prostate cancer aggressiveness using 11C-acetate PET/CT and 1H-MR spectroscopy.

We assessed the ability of 11C-acetate PET/CT, MRI, and proton MR spectroscopy (1H-MRS) to image localized prostate cancer and detect its aggressiveness, using qualitative and quantitative approaches. Methods: Twenty-one patients with untreated localized prostate cancer, diagnosed using transrectal ultrasound-guided biopsy, were prospectively enrolled. Cancer laterality was based on the percentage of cancer and the highest Gleason score determined from biopsies. In addition to PET/CT, 3-dimensional 1H-MRS of the entire prostate volume using a quantitative approach was performed. The imaging and histologic findings of 8 patients undergoing subsequent prostatectomy were compared on a sextant level. For each lobe and sextant, standardized uptake values (SUVs) and (choline + creatine + polyamines)–to–citrate (CCP/C) ratios were obtained from 11C-acetate PET/CT and 1H-MRS, respectively. The visual and quantitative findings on PET/CT and MRI data were compared with cancer laterality and aggressiveness based on the Gleason score and with prostate-specific antigen (PSA) velocity and international risk group classification. Results: The sensitivity, specificity, and accuracy, on a lobar level using visual analysis, of 11C-acetate PET/CT were 80%, 29%, 71%, respectively, and 89%, 29%, 79%, respectively, using contrast-enhanced MRI. The sensitivity and accuracy of 11C-acetate PET/CT decreased to 64% and 63% and specificity increased to 62% when sextant analysis was performed. The agreement between prostate cancer laterality based on biopsy findings and visual interpretation of 11C-acetate PET/CT and contrast-enhanced MRI was similar at 71%. The mean SUV maximum and CCP/C maximum for the dominant tumor lesion were 5.5 and 1.48, respectively, and did not differ significantly from values in the nondominant lobe. The dominant-lesion SUVs or CCP/C values were not associated with histologically determined prostate cancer aggressiveness, nor did PSA velocity correlate with the SUV or CCP/C values from the entire gland. Conclusion: 11C-acetate PET/CT, MRI, and 1H-MRS enable detection of localized prostate cancer with comparable and limited accuracy but fail to provide information on cancer aggressiveness.

Evaluation of different mathematical models for diffusion-weighted imaging of normal prostate and prostate cancer using high b-values: A repeatability study

To evaluate monoexponential, stretched exponential, kurtosis, and biexponential models for diffusion‐weighted imaging (DWI) of normal prostate and prostate cancer (PCa), using b‐values up to 2000 s/mm2, in terms of fitting quality and repeatability.

Automated perfusion‐weighted MRI using localized arterial input functions

To investigate the utility of an automated perfusion‐weighted MRI (PWI) method for estimating cerebral blood flow (CBF) based on localized arterial input functions (AIFs) as compared to the standard method of manual global AIF selection, which is prone to deconvolution errors due to the effects of delay and dispersion of the contrast bolus.

Improved detection of localized prostate cancer using co-registered MRI and 11C-acetate PET/CT.

OBJECTIVES We aimed to study the ability of contrast enhanced MRI at 1.5 T and 11C-acetate PET/CT, both individually and using fused data, to detect localized prostate cancer. METHODS Thirty-six men with untreated prostate cancer and negative for metastatic disease on pelvic CT and bone scan were prospectively enrolled. A pelvic 11C-acetate PET/CT scan was performed in all patients, and a contrast enhanced MRI scan in 33 patients (6 examinations using both endorectal coil and surface coils, and 27 examinations using surface coils only). After the imaging studies 10 patients underwent prostatectomy and 26 were treated by image guided external beam radiation treatment. Image fusion of co-registered PET and MRI data was performed based on anatomical landmarks visible on CT and MRI using an advanced in-house developed software package. PET/CT, MRI and fused PET/MRI data were evaluated visually and compared with biopsy findings on a lobar level, while a sextant approach was used for patients undergoing prostatectomy. RESULTS When using biopsy samples as method of reference, the sensitivity, specificity and accuracy for visual detection of prostate cancer on a lobar level by contrast enhanced MRI was 85%, 37%, 73% and that of 11C-acetate PET/CT 88%, 41%, 74%, respectively. Fusion of PET with MRI data increased sensitivity, specificity and accuracy to 90%, 72% and 85%, respectively. CONCLUSIONS Fusion of sequentially obtained PET/CT and MRI data for the localization of prostate cancer is feasible and superior to the performance of each individual modality alone.

Mathematical models for diffusion-weighted imaging of prostate cancer using b values up to 2000 s/mm2: Correlation with Gleason score and repeatability of region of interest analysis

To evaluate four mathematical models for diffusion weighted imaging (DWI) of prostate cancer (PCa) in terms of PCa detection and characterization.

Optimization of b‐value distribution for biexponential diffusion‐weighted MR imaging of normal prostate

To determine the optimal b‐value distribution for biexponential diffusion‐weighted imaging (DWI) of normal prostate using both a computer modeling approach and in vivo measurements.