Consistency of Renal Stone Volume Measurements Across CT Scanner Model and Reconstruction Algorithm Configurations.

OBJECTIVE: The objective of this prospective study is to evaluate the consistency of renal stone volume estimation using dual-energy CT across scanner model and reconstruction algorithm configurations. SUBJECTS AND METHODS: Patients underwent scanning with routine kidney stone composition protocols on both second- and third-generation dual-source CT scanners. Images were reconstructed using filtered back projection and iterative reconstruction (IR). In addition, a modified IR kernel on the third-generation CT scanner was evaluated. Individual kidney stone volumes were determined and compared. RESULTS: No significant difference was noted in measured volumes between filtered back-projection data, IR data from the second-generation scanner, and the modified IR kernel data (p > 0.05). The third-generation commercially available IR kernel yielded lower volumes than did the other configurations (p < 0.0001). CONCLUSION: With the use of a modified kernel for the third-generation scanner, patients being monitored for changes in kidney stone volume can undergo scanning performed with second- or third-generation dual-energy CT scanners, and the images obtained can be reconstructed with either filtered back projection or IR without the introduction of bias into kidney stone volume measurements.

Radiation Dose Reduction in Pediatric Body CT Using Iterative Reconstruction and a Novel Image-Based Denoising Method.

OBJECTIVE: The objective of this study was to evaluate the radiation dose reduction potential of a novel image-based denoising technique in pediatric abdominopelvic and chest CT examinations and compare it with a commercial iterative reconstruction method. MATERIALS AND METHODS: Data were retrospectively collected from 50 (25 abdominopelvic and 25 chest) clinically indicated pediatric CT examinations. For each examination, a validated noise-insertion tool was used to simulate half-dose data, which were reconstructed using filtered back-projection (FBP) and sinogram-affirmed iterative reconstruction (SAFIRE) methods. A newly developed denoising technique, adaptive nonlocal means (aNLM), was also applied. For each of the 50 patients, three pediatric radiologists evaluated four datasets: full dose plus FBP, half dose plus FBP, half dose plus SAFIRE, and half dose plus aNLM. For each examination, the order of preference for the four datasets was ranked. The organ-specific diagnosis and diagnostic confidence for five primary organs were recorded. RESULTS: The mean (± SD) volume CT dose index for the full-dose scan was 5.3 ± 2.1 mGy for abdominopelvic examinations and 2.4 ± 1.1 mGy for chest examinations. For abdominopelvic examinations, there was no statistically significant difference between the half dose plus aNLM dataset and the full dose plus FBP dataset (3.6 ± 1.0 vs 3.6 ± 0.9, respectively; p = 0.52), and aNLM performed better than SAFIRE. For chest examinations, there was no statistically significant difference between the half dose plus SAFIRE and the full dose plus FBP (4.1 ± 0.6 vs 4.2 ± 0.6, respectively; p = 0.67), and SAFIRE performed better than aNLM. For all organs, there was more than 85% agreement in organ-specific diagnosis among the three half-dose configurations and the full dose plus FBP configuration. CONCLUSION: Although a novel image-based denoising technique performed better than a commercial iterative reconstruction method in pediatric abdominopelvic CT examinations, it performed worse in pediatric chest CT examinations. A 50% dose reduction can be achieved while maintaining diagnostic quality.

Radiation Dose Reduction in Dual-Energy CT: Does It Affect the Accuracy of Urinary Stone Characterization?

OBJECTIVE: The purpose of this article is to assess the effect of radiation dose reduction in dual-energy CT (DECT) on the performance of renal stone characterization using a patient cohort. MATERIALS AND METHODS: CT data from 39 unenhanced DECT examinations performed for stone characterization were retrospectively analyzed in this study. Reduced-dose images were simulated at 75%, 50%, and 25% of the routine dose using a previously validated noise-insertion algorithm. Differentiation between uric acid (UA) and non-UA stones was performed using a fixed cutoff value for the dual-energy ratio. ROC analysis was performed to determine optimal cutoff values and the associated sensitivity and specificity. RESULTS: Of the 206 stones found, 43 were UA and 163 were non-UA. The mean (± SD) volume CT dose index (CTDIvol) was 16.0 ± 4.0 mGy at the 100% dose level. The mean noise in 100-kV images increased from 40.9 ± 6.8 HU at 100% dose to 46.8 ± 8.8 HU, 57.7 ± 12.5 HU, and 85.4 ± 22.9 HU at 75%, 50%, and 25% dose levels, respectively. Using the default cutoff value, for stones 10 mm(3) or larger, the sensitivity/specificity were 100.0%/98.8%, 82.8%/98.8%, and 89.3%/98.7%, at 75%, 50%, and 25% dose levels, respectively. ROC analysis showed varying optimal cutoff values at different dose levels. The sensitivity and specificity improved with use of these optimal cutoff values. Differentiation capability decreased for stones smaller than 10 mm(3). CONCLUSION: At 75% of the 16-mGy routine dose, the sensitivity and specificity for differentiating UA from non-UA stones were minimally affected for stones 10 mm(3) or larger. The use of optimal cutoff values for dual-energy ratio as dose decreased (and noise increased) provided improved performance.

Observer Performance in the Detection and Classification of Malignant Hepatic Nodules and Masses with CT Image-Space Denoising and Iterative Reconstruction.

PURPOSE: To determine if lower-dose computed tomographic (CT) scans obtained with adaptive image-based noise reduction (adaptive nonlocal means [ANLM]) or iterative reconstruction (sinogram-affirmed iterative reconstruction [SAFIRE]) result in reduced observer performance in the detection of malignant hepatic nodules and masses compared with routine-dose scans obtained with filtered back projection (FBP). MATERIALS AND METHODS: This study was approved by the institutional review board and was compliant with HIPAA. Informed consent was obtained from patients for the retrospective use of medical records for research purposes. CT projection data from 33 abdominal and 27 liver or pancreas CT examinations were collected (median volume CT dose index, 13.8 and 24.0 mGy, respectively). Hepatic malignancy was defined by progression or regression or with histopathologic findings. Lower-dose data were created by using a validated noise insertion method (10.4 mGy for abdominal CT and 14.6 mGy for liver or pancreas CT) and images reconstructed with FBP, ANLM, and SAFIRE. Four readers evaluated routine-dose FBP images and all lower-dose images, circumscribing liver lesions and selecting diagnosis. The jackknife free-response receiver operating characteristic figure of merit (FOM) was calculated on a per-malignant nodule or per-mass basis. Noninferiority was defined by the lower limit of the 95% confidence interval (CI) of the difference between lower-dose and routine-dose FOMs being less than -0.10. RESULTS: Twenty-nine patients had 62 malignant hepatic nodules and masses. Estimated FOM differences between lower-dose FBP and lower-dose ANLM versus routine-dose FBP were noninferior (difference: -0.041 [95% CI: -0.090, 0.009] and -0.003 [95% CI: -0.052, 0.047], respectively). In patients with dedicated liver scans, lower-dose ANLM images were noninferior (difference: +0.015 [95% CI: -0.077, 0.106]), whereas lower-dose FBP images were not (difference -0.049 [95% CI: -0.140, 0.043]). In 37 patients with SAFIRE reconstructions, the three lower-dose alternatives were found to be noninferior to the routine-dose FBP. CONCLUSION: At moderate levels of dose reduction, lower-dose FBP images without ANLM or SAFIRE were noninferior to routine-dose images for abdominal CT but not for liver or pancreas CT.

Observer performance for adaptive, image-based denoising and filtered back projection compared to scanner-based iterative reconstruction for lower dose CT enterography.

PURPOSE: The purpose of this study was to compare observer performance for detection of intestinal inflammation for low-dose CT enterography (LD-CTE) using scanner-based iterative reconstruction (IR) vs. vendor-independent, adaptive image-based noise reduction (ANLM) or filtered back projection (FBP). METHODS: Sixty-two LD-CTE exams were performed. LD-CTE images were reconstructed using IR, ANLM, and FBP. Three readers, blinded to image type, marked intestinal inflammation directly on patient images using a specialized workstation over three sessions, interpreting one image type/patient/session. Reference standard was created by a gastroenterologist and radiologist, who reviewed all available data including dismissal Gastroenterology records, and who marked all inflamed bowel segments on the same workstation. Reader and reference localizations were then compared. Non-inferiority was tested using Jackknife free-response ROC (JAFROC) figures of merit (FOM) for ANLM and FBP compared to IR. Patient-level analyses for the presence or absence of inflammation were also conducted. RESULTS: There were 46 inflamed bowel segments in 24/62 patients (CTDIvol interquartile range 6.9-10.1 mGy). JAFROC FOM for ANLM and FBP were 0.84 (95% CI 0.75-0.92) and 0.84 (95% CI 0.75-0.92), and were statistically non-inferior to IR (FOM 0.84; 95% CI 0.76-0.93). Patient-level pooled confidence intervals for sensitivity widely overlapped, as did specificities. Image quality was rated as better with IR and AMLM compared to FBP (p < 0.0001), with no difference in reading times (p = 0.89). CONCLUSIONS: Vendor-independent adaptive image-based noise reduction and FBP provided observer performance that was non-inferior to scanner-based IR methods. Adaptive image-based noise reduction maintained or improved upon image quality ratings compared to FBP when performing CTE at lower dose levels.

Size-specific Dose Estimates for Chest, Abdominal, and Pelvic CT: Effect of Intrapatient Variability in Water-equivalent Diameter.

PURPOSE: To develop software to automatically calculate size-specific dose estimates (SSDEs) and to assess the effect of variations in water-equivalent diameter (Dw) along the z-axis on SSDE for computed tomographic (CT) examinations of the torso. MATERIALS AND METHODS: In this institutional review board-approved, HIPAA-compliant, retrospective study, a software program was used to calculate Dw at each image position in 102 consecutive CT examinations of the combined chest, abdomen, and pelvis. SSDE was calculated by multiplying the size-dependent conversion factor and volume CT dose index (CTDIvol) at each image position. The variations in Dw along the z-axis were determined for six hypothetical scanning ranges: chest alone; abdomen alone; pelvis alone; chest and abdomen; abdomen and pelvis; and chest, abdomen, and pelvis. Mean SSDE was calculated in two ways: (a) from the SSDE at each position and (b) from the mean CTDIvol over each scan range and the conversion factor corresponding to Dw at the middle of the scan range. Linear regression analysis was performed to determine the correlation between SSDE values calculated in these two ways. RESULTS: Across patients, for scan ranges 1-6, the mean of the difference between maximal and minimal Dw within a given patient was 5.2, 4.9, 2.5, 6.0, 5.6, and 6.5 cm, respectively. The mean SSDE values calculated by using the two methods were in close agreement, with root mean square differences of 0.9, 0.5, 0.5, 1.4, 1.0, and 1.1 mGy or 6%, 3%, 2%, 9%, 4%, and 6%, for the scan ranges of chest; abdomen; pelvis; chest and abdomen; abdomen and pelvis; and chest, abdomen, and pelvis, respectively. CONCLUSION: Using the mean CTDIvol from the whole scan range and Dw from the image at the center of the scan range provided an easily obtained estimate of SSDE for the whole scan range that agreed well with values from an image-by-image approach, with a root mean square difference less than 1.4 mGy (9%).

Feasibility of discriminating uric acid from non-uric acid renal stones using consecutive spatially registered low- and high-energy scans obtained on a conventional CT scanner.

OBJECTIVE: The objective of our study was to show the feasibility of distinguishing between uric acid (UA) and non-UA renal stones using two consecutive spatially registered low- and high-energy scans acquired on a conventional CT system. SUBJECTS AND METHODS: A total of 33 patients undergoing clinically indicated dual-source dual-energy CT examinations to differentiate UA from non-UA renal stones were enrolled in this study. Immediately after patients underwent clinically indicated dual-source dual-energy CT, two consecutive scans (one at 80 kV and one at 140 kV) were obtained on a conventional CT scanner over the region limited to the stones identified on the dual-source scans. After 3D deformable registration of the 80- and 140-kV images, UA and non-UA stones were identified using commercial software. The sensitivity, specificity, and accuracy of stone classification were calculated using the dual-source results as the reference standard. RESULTS: A total of 469 stones were identified in the dual-source examinations (26 UA and 443 non-UA stones). The average in-plane stone diameter was 4.4 ± 2.5 (SD) mm (range, 2.0-18.9 mm). The overall sensitivity, specificity, and accuracy for identifying UA stones were 73.1%, 90.1%, and 89.1%, respectively. The sensitivity, specificity, and accuracy were 94.7%, 96.9%, and 96.8% for stones 3 mm or larger (n = 341 [19 UA and 322 non-UA]). CONCLUSION: Accurate differentiation of UA from non-UA renal stones is feasible using two consecutively acquired and spatially registered conventional CT scans.

Methods for clinical evaluation of noise reduction techniques in abdominopelvic CT.

Most noise reduction methods involve nonlinear processes, and objective evaluation of image quality can be challenging, since image noise cannot be fully characterized on the sole basis of the noise level at computed tomography (CT). Noise spatial correlation (or noise texture) is closely related to the detection and characterization of low-contrast objects and may be quantified by analyzing the noise power spectrum. High-contrast spatial resolution can be measured using the modulation transfer function and section sensitivity profile and is generally unaffected by noise reduction. Detectability of low-contrast lesions can be evaluated subjectively at varying dose levels using phantoms containing low-contrast objects. Clinical applications with inherent high-contrast abnormalities (eg, CT for renal calculi, CT enterography) permit larger dose reductions with denoising techniques. In low-contrast tasks such as detection of metastases in solid organs, dose reduction is substantially more limited by loss of lesion conspicuity due to loss of low-contrast spatial resolution and coarsening of noise texture. Existing noise reduction strategies for dose reduction have a substantial impact on lowering the radiation dose at CT. To preserve the diagnostic benefit of CT examination, thoughtful utilization of these strategies must be based on the inherent lesion-to-background contrast and the anatomy of interest. The authors provide an overview of existing noise reduction strategies for low-dose abdominopelvic CT, including analytic reconstruction, image and projection space denoising, and iterative reconstruction; review qualitative and quantitative tools for evaluating these strategies; and discuss the strengths and limitations of individual noise reduction methods.

Reducing image noise in computed tomography (CT) colonography: effect of an integrated circuit CT detector.

OBJECTIVE: To investigate whether the integrated circuit (IC) detector results in reduced noise in computed tomography (CT) colonography (CTC). METHODS: Three hundred sixty-six consecutive patients underwent clinically indicated CTC using the same CT scanner system, except for a difference in CT detectors (IC or conventional). Image noise, patient size, and scanner radiation output (volume CT dose index) were quantitatively compared between patient cohorts using each detector system, with separate comparisons for the abdomen and pelvis. RESULTS: For the abdomen and pelvis, despite significantly larger patient sizes in the IC detector cohort (both P < 0.001), image noise was significantly lower (both P < 0.001), whereas volume CT dose index was unchanged (both P > 0.18). Based on the observed image noise reduction, radiation dose could alternatively be reduced by approximately 20% to result in similar levels of image noise. CONCLUSION: Computed tomography colonography images acquired using the IC detector had significantly lower noise than images acquired using the conventional detector. This noise reduction can permit further radiation dose reduction in CTC.

Automatic selection of tube potential for radiation dose reduction in vascular and contrast-enhanced abdominopelvic CT.

OBJECTIVE: The purpose of this study is to assess the ability of a novel automatic tube potential selection tool to reduce radiation dose while maintaining diagnostic quality in CT angiography (CTA) and contrast-enhanced abdominopelvic CT. MATERIALS AND METHODS: One hundred one CTA examinations and 90 contrastenhanced abdominopelvic examinations were performed using an automatic tube potential selection tool on a 128-MDCT scanner. Two vascular radiologists and two abdominal radiologists evaluated the image quality for sharpness, noise, artifact, and diagnostic confidence. In a subset of patients who had undergone prior studies (CTA, 28 patients; abdominopelvic CT, 25 patients), a side-by-side comparison was performed by a separate radiologist. Dose reduction and iodine contrast-to-noise ratio resulting from use of the tool were calculated. RESULTS: For CTA, 80 or 100 kV was selected for 73% of the scans, with a mean dose reduction of 36% relative to the reference 120-kV protocol. For abdominopelvic CT examinations, 80 or 100 kV was used for 55% of the scans, with a mean dose reduction of 25%. Overall dose reduction relative to the reference 120-kV protocol was 25% and 13% for CTA and abdominopelvic CT scans, respectively. Over 98% of scans had acceptable sharpness, noise texture, artifact, and diagnostic confidence for both readers and diagnostic tasks; 94-100% of scans had acceptable noise. Iodine contrast-to-noise ratio was significantly higher than (p < 0.001) or similar to (p = 0.11) that of prior scans, and equivalent quality was achieved despite the dose reduction. CONCLUSION: Automatic tube potential selection provides an efficient and quantitativeway to guide the selection of the optimal tube potential for CTA and abdominopelvic CT examinations.

Individualization of abdominopelvic CT protocols with lower tube voltage to reduce i.v. contrast dose or radiation dose.

OBJECTIVE: The purpose of this study was to validate an individualized approach to contrast-enhanced body CT using size-specific tube potential selection to reduce either i.v. contrast or radiation dose while maintaining diagnostic image quality. MATERIALS AND METHODS: With a validated noise insertion method and retrospective image quality assessment (scale 1-5, ≥ 3 acceptable), the lowest acceptable iodine contrast-to-noise ratio (CNR) was determined for 25 body CT examinations. Age-appropriate CT protocols with size-specific tube potential selection were then developed to accomplish two goals: i.v. contrast dose reduction for patients 50 years old and older and radiation dose reduction for patients younger than 50 years. After implementation, subjective and objective image quality metrics were retrospectively compared between the individualized scans and previous fixed-tube-potential scans. RESULTS: Diagnostically acceptable iodine CNR was achieved with use of up to 40% dose reduction from the baseline protocol. At this dose level, results of logistic regression analysis predicted 94% probability of acceptable image quality. With the individualized protocols that targeted this iodine CNR, 84 patients 50 years old and older had a mean i.v. contrast dose reduction of 26% (100.9 ± 20.7 mL vs 136.2 ± 24.9 mL; p < 0.001) with unchanged image quality scores (4.6 ± 0.5 vs 4.6 ± 0.4; p = 0.160). Thirty patients younger than 50 years had a mean radiation dose reduction of 41% (mean volume CT dose index, 11.6 ± 5.3 mGy vs 19.7 ± 7.8 mGy; p < 0.001) with acceptable but slightly reduced mean image quality scores (4.1 ± 0.4 vs 4.7 ± 0.4; p < 0.001). CONCLUSION: With the use of age-appropriate scan protocols and size-specific selection of tube potential, acceptable image quality can be maintained while i.v. contrast dose or radiation dose is substantially lowered.

Pilot study of detection, radiologist confidence and image quality with sinogram-affirmed iterative reconstruction at half-routine dose level.

OBJECTIVE: The objective of this study was to determine the effect of Sinogram-Affirmed Iterative Reconstruction (SAFIRE) on radiological detection, diagnostic confidence, and image quality at half-dose, contrast-enhanced abdominopelvic computed tomography. METHODS: Forty dual-source examinations were reconstructed using routine-dose with filtered back projection, half-dose filtered back projection, and half-dose SAFIRE. Three radiologists detected lesions in abdominopelvic organs, reporting findings of potential medical significance, diagnostic confidence, and image quality. RESULTS: There was greater than 78% concordance between full- and half-dose images ± SAFIRE, and no difference in the detection of lesions within organs between half-dose images ± SAFIRE (P = 0.22 - 1.0). Detection of potentially important findings varied by reader, but not between dose/reconstruction methods. Diagnostic confidence varied widely (P < 0.001 to P > 0.91). Sinogram-Affirmed Iterative Reconstruction significantly improved image quality in the pelvis (P ≤ 0.04). CONCLUSIONS: Half-dose images ± SAFIRE had organ-specific detections similar to routine-dose images. Sinogram-Affirmed Iterative Reconstruction improved image quality in the pelvis, but diagnostic confidence and image quality scores in the abdomen depended on the reader.

Validation of dual-source single-tube reconstruction as a method to obtain half-dose images to evaluate radiation dose and noise reduction: phantom and human assessment using CT colonography and sinogram-affirmed iterative reconstruction (SAFIRE).

OBJECTIVE: To evaluate a method for obtaining half-dose CT images for observer studies evaluating lower-dose CT. METHODS: Phantoms of varying sizes were scanned at multiple tube potentials using dose-matched dual-source (DS) and single-source (SS) protocols. Images from single-tube reconstruction of DS data were compared with SS images acquired at half-original CTDIvol. Thirty patients underwent supine SS and dose-matched prone DS CT colonography (CTC). Half-dose prone images were reconstructed with sinogram-affirmed iterative reconstruction (SAFIRE). Two radiologists scored image quality on 2-dimensional (2D) and 3D images. RESULTS: Image noise was similar between half-dose SS images and DS images reconstructed from one tube only with tube potential of 120 kV or more for phantoms 40 cm or smaller (P < 0.05). For both readers, the patients' CTC image quality scores were more than 84% concordant between SS or DS CTC images, and half-dose-prone CTC images with SAFIRE had 84% or more concordance with routine-dose CTC except for 3D image noise. CONCLUSIONS: In appropriately sized patients, DS acquisition with single-tube reconstruction can create half-dose images, permitting comparison to full-dose images. For CTC, there is comparable image quality for colonic evaluation between full-dose and half-dose images reconstructed with SAFIRE.

Development and validation of a practical lower-dose-simulation tool for optimizing computed tomography scan protocols.

OBJECTIVE: The objective of this study was to develop and validate a novel noise insertion method that can accurately simulate lower-dose images from existing standard-dose computed tomography (CT) data. METHODS: The noise insertion method incorporates the effects of the bowtie filter, automatic exposure control, and electronic noise. We validated this tool using both phantom and patient studies. The phantom study compared simulated lower-dose images with the actually acquired lower-dose images. The patient studies included 105 pediatric and 24 adult CT body examinations. RESULTS: The noise level in the simulated images was within 3.2% of the actual lower-dose images in phantom experiments. Noise power spectrum also demonstrated excellent agreement. For the patient examinations, a mean difference of noise level between 2.0% and 9.7% was observed for simulated dose levels between 75% and 30% of the original dose. CONCLUSIONS: An accurate technique for simulating lower-dose CT images was developed and validated, which can be used to retrospectively optimize CT protocols.

Alzheimer disease-like phenotype associated with the c.154delA mutation in progranulin.

OBJECTIVE: To characterize a kindred with a familial neurodegenerative disorder associated with a mutation in progranulin (PGRN), with emphasis on the unique clinical features in this kindred. DESIGN: Antemortem and postmortem characterization of a kindred with a familial neurodegenerative disorder. SETTING: Multispecialty group academic medical center. PATIENTS: Affected members of a kindred with dementia with or without parkinsonism associated with a unique mutation in PGRN. MAIN OUTCOME MEASURE: Genotype-phenotype correlation. RESULTS: Of 10 affected individuals identified, 6 presented with early amnestic symptoms which resulted in initial diagnoses of Alzheimer disease or amnestic mild cognitive impairment. Some individuals presented with features characteristic of frontotemporal dementia. Mean age at onset was substantially younger in generation III (75.8 years; range, 69-80 years) than in generation II (60.7 years; range, 55-66 years). The pattern of cerebral atrophy varied widely in the affected individuals. Neuropathologic features in 6 individuals included frontotemporal lobar degeneration with ubiquitin-positive neuronal cytoplasmic and intranuclear inclusions (FTLD-U with NII). PGRN analysis revealed a single base pair deletion in exon 2 (c.154delA), which caused a frameshift (p.Thr52HisfsX2) and, therefore, creation of a premature termination codon and a likely null allele. CONCLUSIONS: In this large kindred, most affected individuals had clinical presentations that resembled Alzheimer disease or amnestic mild cognitive impairment associated with a mutation in PGRN and underlying FTLD-U with NII neuropathologic abnormalities. This finding is in distinct contrast to previously reported kindreds, in which clinical presentations have typically been within the spectrum of FTLD. The basis for the large difference in age at onset between generations requires further study.

Mild cognitive impairment associated with limbic and neocortical Lewy body disease: a clinicopathological study.

There are little data on the relationship between Lewy body disease and mild cognitive impairment syndromes. The Mayo Clinic aging and dementia databases in Rochester, Minnesota, and Jacksonville, Florida were queried for cases who were diagnosed with mild cognitive impairment between 1 January 1996 and 30 April 2008, were prospectively followed and were subsequently found to have autopsy-proven Lewy body disease. The presence of rapid eye movement sleep behaviour disorder was specifically assessed. Mild cognitive impairment subtypes were determined by clinical impression and neuropsychological profiles, based on prospective operational criteria. The diagnosis of clinically probable dementia with Lewy bodies was based on the 2005 McKeith criteria. Hippocampal volumes, rate of hippocampal atrophy, and proton magnetic resonance spectroscopy were assessed on available magnetic resonance imaging and spectroscopy scans. Eight subjects were identified; six were male. Seven developed dementia with Lewy bodies prior to death; one died characterized as mild cognitive impairment. The number of cases and median age of onset (range) for specific features were: seven with rapid eye movement sleep behaviour disorder-60 years (27-91 years), eight with cognitive symptoms-69 years (62-89 years), eight with mild cognitive impairment-70.5 years (66-91 years), eight with parkinsonism symptoms-71 years (66-92 years), six with visual hallucinations-72 years (64-90 years), seven with dementia-75 years (67-92 years), six with fluctuations in cognition and/or arousal-76 years (68-92 years) and eight dead-76 years (71-94 years). Rapid eye movement sleep behaviour disorder preceded cognitive symptom onset in six cases by a median of 10 years (2-47 years) and mild cognitive impairment diagnosis by a median of 12 years (3-48 years). The mild cognitive impairment subtypes represented include: two with single domain non-amnestic mild cognitive impairment, three with multi-domain non-amnestic mild cognitive impairment, and three with multi-domain amnestic mild cognitive impairment. The cognitive domains most frequently affected were attention and executive functioning, and visuospatial functioning. Hippocampal volumes and the rate of hippocampal atrophy were, on average, within the normal range in the three cases who underwent magnetic resonance imaging, and the choline/creatine ratio was elevated in the two cases who underwent proton magnetic resonance spectroscopy when they were diagnosed as mild cognitive impairment. On autopsy, six had neocortical-predominant Lewy body disease and two had limbic-predominant Lewy body disease; only one had coexisting high-likelihood Alzheimer's disease. These findings indicate that among Lewy body disease cases that pass through a mild cognitive impairment stage, any cognitive pattern or mild cognitive subtype is possible, with the attention/executive and visuospatial domains most frequently impaired. Hippocampal volume and proton magnetic resonance spectroscopy data were consistent with recent data in dementia with Lewy bodies. All cases with rapid eye movement sleep behaviour disorder and mild cognitive impairment were eventually shown to have autopsy-proven Lewy body disease, indicating that rapid eye movement sleep behaviour disorder plus mild cognitive impairment probably reflects brainstem and cerebral Lewy body disease.

Distinct anatomical subtypes of the behavioural variant of frontotemporal dementia: a cluster analysis study.

The behavioural variant of frontotemporal dementia is a progressive neurodegenerative syndrome characterized by changes in personality and behaviour. It is typically associated with frontal lobe atrophy, although patterns of atrophy are heterogeneous. The objective of this study was to examine case-by-case variability in patterns of grey matter atrophy in subjects with the behavioural variant of frontotemporal dementia and to investigate whether behavioural variant of frontotemporal dementia can be divided into distinct anatomical subtypes. Sixty-six subjects that fulfilled clinical criteria for a diagnosis of the behavioural variant of frontotemporal dementia with a volumetric magnetic resonance imaging scan were identified. Grey matter volumes were obtained for 26 regions of interest, covering frontal, temporal and parietal lobes, striatum, insula and supplemental motor area, using the automated anatomical labelling atlas. Regional volumes were divided by total grey matter volume. A hierarchical agglomerative cluster analysis using Ward's clustering linkage method was performed to cluster the behavioural variant of frontotemporal dementia subjects into different anatomical clusters. Voxel-based morphometry was used to assess patterns of grey matter loss in each identified cluster of subjects compared to an age and gender-matched control group at P < 0.05 (family-wise error corrected). We identified four potentially useful clusters with distinct patterns of grey matter loss, which we posit represent anatomical subtypes of the behavioural variant of frontotemporal dementia. Two of these subtypes were associated with temporal lobe volume loss, with one subtype showing loss restricted to temporal lobe regions (temporal-dominant subtype) and the other showing grey matter loss in the temporal lobes as well as frontal and parietal lobes (temporofrontoparietal subtype). Another two subtypes were characterized by a large amount of frontal lobe volume loss, with one subtype showing grey matter loss in the frontal lobes as well as loss of the temporal lobes (frontotemporal subtype) and the other subtype showing loss relatively restricted to the frontal lobes (frontal-dominant subtype). These four subtypes differed on clinical measures of executive function, episodic memory and confrontation naming. There were also associations between the four subtypes and genetic or pathological diagnoses which were obtained in 48% of the cohort. The clusters did not differ in behavioural severity as measured by the Neuropsychiatric Inventory; supporting the original classification of the behavioural variant of frontotemporal dementia in these subjects. Our findings suggest behavioural variant of frontotemporal dementia can therefore be subdivided into four different anatomical subtypes.

Comparison of 18F-FDG and PiB PET in cognitive impairment.

UNLABELLED: The purpose of this study was to compare the diagnostic accuracy of glucose metabolism and amyloid deposition as demonstrated by (18)F-FDG and Pittsburg Compound B (PiB) PET to evaluate subjects with cognitive impairment. METHODS: Subjects were selected from existing participants in the Mayo Alzheimer's Disease Research Center or Alzheimer's Disease Patient Registry programs. A total of 20 healthy controls and 17 amnestic mild cognitive impairment (aMCI), 6 nonamnestic mild cognitive impairment (naMCI), and 13 Alzheimer disease (AD) subjects were imaged with both PiB and (18)F-FDG PET between March 2006 and August 2007. Global measures for PiB and (18)F-FDG PET uptake, normalized to cerebellum for PiB and pons for (18)F-FDG, were compared. Partial-volume correction, standardized uptake value (SUV), and cortical ratio methods of image analysis were also evaluated in an attempt to optimize the analysis for each test. RESULTS: Significant discrimination (P < 0.05) between controls and AD, naMCI and aMCI, naMCI and AD, and aMCI and AD by PiB PET measurements was observed. The paired groupwise comparisons of the global measures demonstrated that PiB PET versus (18)F-FDG PET showed similar significant group separation, with only PiB showing significant separation of naMCI and aMCI subjects. CONCLUSION: PiB PET and (18)F-FDG PET have similar diagnostic accuracy in early cognitive impairment. However, significantly better group discrimination in naMCI and aMCI subjects by PiB, compared with (18)F-FDG, was seen and may suggest early amyloid deposition before cerebral metabolic disruption in this group.

Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer's disease: implications for sequence of pathological events in Alzheimer's disease.

The purpose of this study was to use serial imaging to gain insight into the sequence of pathologic events in Alzheimer's disease, and the clinical features associated with this sequence. We measured change in amyloid deposition over time using serial (11)C Pittsburgh compound B (PIB) positron emission tomography and progression of neurodegeneration using serial structural magnetic resonance imaging. We studied 21 healthy cognitively normal subjects, 32 with amnestic mild cognitive impairment and 8 with Alzheimer's disease. Subjects were drawn from two sources--ongoing longitudinal registries at Mayo Clinic, and the Alzheimer's disease Neuroimaging Initiative (ADNI). All subjects underwent clinical assessments, MRI and PIB studies at two time points, approximately one year apart. PIB retention was quantified in global cortical to cerebellar ratio units and brain atrophy in units of cm(3) by measuring ventricular expansion. The annual change in global PIB retention did not differ by clinical group (P = 0.90), and although small (median 0.042 ratio units/year overall) was greater than zero among all subjects (P < 0.001). Ventricular expansion rates differed by clinical group (P < 0.001) and increased in the following order: cognitively normal (1.3 cm(3)/year) < amnestic mild cognitive impairment (2.5 cm(3)/year) < Alzheimer's disease (7.7 cm(3)/year). Among all subjects there was no correlation between PIB change and concurrent change on CDR-SB (r = -0.01, P = 0.97) but some evidence of a weak correlation with MMSE (r =-0.22, P = 0.09). In contrast, greater rates of ventricular expansion were clearly correlated with worsening concurrent change on CDR-SB (r = 0.42, P < 0.01) and MMSE (r =-0.52, P < 0.01). Our data are consistent with a model of typical late onset Alzheimer's disease that has two main features: (i) dissociation between the rate of amyloid deposition and the rate of neurodegeneration late in life, with amyloid deposition proceeding at a constant slow rate while neurodegeneration accelerates and (ii) clinical symptoms are coupled to neurodegeneration not amyloid deposition. Significant plaque deposition occurs prior to clinical decline. The presence of brain amyloidosis alone is not sufficient to produce cognitive decline, rather, the neurodegenerative component of Alzheimer's disease pathology is the direct substrate of cognitive impairment and the rate of cognitive decline is driven by the rate of neurodegeneration. Neurodegeneration (atrophy on MRI) both precedes and parallels cognitive decline. This model implies a complimentary role for MRI and PIB imaging in Alzheimer's disease, with each reflecting one of the major pathologies, amyloid dysmetabolism and neurodegeneration.