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IMPAIRED CSF CLEARANCE AND BRAIN AMYLOID IN ALZHEIMER'S DISEASE: A MULTI-TRACER PET STUDY
Li, Yi; DeLeon, Mony J; Tsui, Wai; Pirraglia, Elizabeth; Glodzik, Lidia; Chen, Jingyun; Osorio, Ricardo S; Rusinek, Henry
ORIGINAL:0013084
ISSN: 1552-5279
CID: 3386632
REnal Flow and Microstructure AnisotroPy (REFMAP) MRI in Normal and Peritumoral Renal Tissue
Liu, Andrea L; Mikheev, Artem; Rusinek, Henry; Huang, William C; Wysock, James S; Babb, James S; Feiweier, Thorsten; Stoffel, David; Chandarana, Hersh; Sigmund, Eric E
BACKGROUND:Diffusion-weighted imaging (DWI) provides insight into the pathophysiology underlying renal dysfunction. Variants of DWI include intravoxel incoherent motion (IVIM), which differentiates between microstructural diffusion and vascular or tubular flow, and diffusion tensor imaging (DTI), which quantifies diffusion directionality. PURPOSE/OBJECTIVE:To investigate the reproducibility of joint IVIM-DTI and compare controls to presurgical renal mass patients. STUDY TYPE/METHODS:Prospective cross-sectional. SUBJECTS/METHODS:Thirteen healthy controls and ten presurgical renal mass patients were scanned. Ten controls were scanned twice to investigate reproducibility. FIELD STRENGTH/SEQUENCE/UNASSIGNED:Subjects were scanned on a 3T system using 10 b-values and 20 diffusion directions for IVIM-DTI in a study approved by the local Institutional Review Board. ASSESSMENT/RESULTS:Retrospective coregistration and measurement of joint IVIM-DTI parameters were performed. STATISTICAL ANALYSIS/METHODS:Parameter reproducibility was defined as intraclass correlation coefficient (ICC) >0.7 and coefficient of variation (CV) <30%. Patient data were stratified by lesion side (contralateral/ipsilateral) for comparison with controls. Corticomedullary differentiation was evaluated. RESULTS:In controls, the reproducible subset of REnal Flow and Microstructure AnisotroPy (REFMAP) parameters had average ICC = 0.82 and CV = 7.5%. In renal mass patients, medullary fractional anisotropy (FA) was significantly lower than in controls (0.227 ± 0.072 vs. 0.291 ± 0.044, P = 0.016 for the kidney contralateral to the mass and 0.228 ± 0.070 vs. 0.291 ± 0.044, P = 0.018 for the kidney ipsilateral). In the kidney ipsilateral to the mass, cortical Dp,radial was significantly higher than in controls (P = 0.012). Conversely, medullary Dp,axial was significantly lower in contralateral than ipsilateral kidneys (P = 0.027) and normal controls (P = 0.044). DATA CONCLUSION/UNASSIGNED:REFMAP-MRI parameters provide unique information regarding renal dysfunction. In presurgical renal mass patients, directional flow changes were noted that were not identified with IVIM analysis alone. Both contralateral and ipsilateral kidneys in patients show reductions in structural diffusivities and anisotropy, while flow metrics showed opposing changes in contralateral vs. ipsilateral kidneys. LEVEL OF EVIDENCE/METHODS:2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.
PMCID:6030440
PMID: 29331053
ISSN: 1522-2586
CID: 2906262
Quantitative evaluation of tau PET tracers 18F-THK5351 and 18F-AV-1451 in Alzheimer's disease with standardized uptake value peak-alignment (SUVP) normalization
Chen, Jingyun; Li, Yi; Pirraglia, Elizabeth; Okamura, Nobuyuki; Rusinek, Henry; de Leon, Mony J
PURPOSE/OBJECTIVE:F-THK5351. The conventional standardized uptake value ratio (SUVR) method relies on the average uptake from an unaffected tissue sample, and therefore is susceptible to biases from off-target binding as well as variability among individuals in the reference region. We propose a new method, standardized uptake value peak-alignment (SUVP), to reduce the bias of the SUVR, and improve the quantitative assessment of tau deposition. METHODS:F-AV-1451 on two independent cohorts (N = 18 and 32, respectively), each with cognitively normal (NL) subjects and Alzheimer's disease (AD) subjects. RESULTS:F-AV-1451). In the cerebellar cortex, an AD-NL group difference with effect size (Cohen's d) of 0.62 was observed for AV-1451, confirming the limitation of the SUVR approach using this region as a reference. A smaller cerebellar effect size (0.09) was observed for THK5351. CONCLUSION/CONCLUSIONS:The SUVP method reduces the bias of the reference region and improves the NL-AD classification compared to the SUVR approach.
PMID: 29704038
ISSN: 1619-7089
CID: 3149532
Segmentation of breast from T1-weighted MRI: Error analysis [Meeting Abstract]
Rusinek, H; Mikheev, A; Heacock, L; Melsaether, A; Moy, L
Purpose Our aim was to evaluate the accuracy of a new algorithm to automatically delineate the breast region from the chest on T1-weighted, non-fat-suppressed MR images. This process is also referred to as the chest wall detection. There is a general agreement that this step is very difficult to automate. At the same time it is crucially needed for clinically important processing workflows [1]. These workflows include 3D measurement of breast density and of the breast parenchymal enhancement. Both measures reveal patients at risk of breast cancer [2]. Manually traced chest wall was used as the ground truth when estimating the segmentation errors. Segmentation accuracy was evaluated using the Hausdorff distance and the volumetric error. We also estimated the inter-observer agreement in defining the chest wall surface. Methods The program starts by generating the mid-sagittal 2D section by averaging the signal across 20 mm thick mid-sagittal slab. We determine the chest wall boundary on this image by modeling the signal profiles along the antero-posterior direction as a sequence of three tissues: background air, skin and fat layer, muscle. Non-uniformity correction is then applied to the entire 3D volume. The mid-sagittal boundary, represented as a polyline P, is then propagated in two opposite (left and right) directions. At each sagittal section the algorithm adjusts the control points of the polyline received from an adjacent slice. The adjustment is estimated from the weighted sum of six measures that combine specific local and global signal statistics. These include: the local gradient, the signal uniformity, the gradient similarity, the contour-gradient consistency, the global contour uniformity and the normal vector consistency. At each iteration we form a candidate shift vector, we apply it to shift P to its new position, and then we smooth the resulting polyline. The process terminates when the magnitude of the shift becomes negligible or when the specified number of iterations is exceeded. Two metrics were used to estimate accuracy. The conventional volumetric error was obtained by dividing the volume DV of misclassified breast voxels over the true breast volume V. The Hausdorff distance, HD, is the distance between each voxel on the true breast/ chest wall border and the closest boundary voxel produced by the algorithm. HD is averaged over the entire chest wall surface. From a clinical database of screening breast MRIs acquired at our medical center we have randomly selected 16 test exams. The selection was constrained to enforce that there were four exams in each of the four breast density categories [3]. Bilateral breasts were imaged on Siemens 3T Magnetom Trio equipped with a 7-element surface breast coil. The parameters of the T1-weighted non-fat-suppressed sequence were: TR = 4.74 ms, TE = 1.79 ms, FOV = 320 mm2, matrix = 448 9 358 9*150, 0.7 9 0.7 9 1.1 mm voxels, TA = 2-3 min. Three experts in breast and chest anatomy drew contours to separate the chest wall from the breast (Fig. 1). The pectoralis fascia and pectoralis muscles were used as reference points for the anterolateral borders. The medial border of the axilla was the posterolateral boundary. The axillary tail was considered as the breast tissue. The ground truth references were constructed by a software designed to perform voxel-based ROI averaging [4]. (Figure Presented) Results The border distance error HD was 0.84 +/- 0.8 mm (average +/- standard deviation) and ranged from 0.57 to 2.45 mm. The volume error DV/V was 6.43 +/- 6.82%. There was no correlation between the HD and DV/V (R2 = 0.23, p = 0.12). The test cases covered a wide range 411-3439 ml of breast volumes. There was a significant positive correlation (R2 = 0.40, p = 0.02) between volumetric error and the true breast volume V, but there was no correlation between HD and V (R2 = 0.08, p = 0.44). The average execution time was under 1.5 min per case on a standard 8-core workstation. The inter-observer agreement measured in term of HD was 0.56 +/- 0.15 mm (average +/- standard deviation). The agreement expressed in terms of volumetric discrepancy (relative to breast volume) was 1.61% +/- 0.71%. Conclusion Breast density, defined as fraction of fibroglandular tissue, and postcontrast enhancement, are considered significant risk factors for breast cancer. These MRI measures are recommended for radiologic reports and are promising cancer biomarkers. Radiologists currently visually estimate these measure. Unfortunately, readers agreement for qualitative evaluation is only fair, requiring better standardization and reproducibility. Computer-assisted quantitative assessment is needed, but the task is challenging due to image nonuniformity (breast coils cause loss of MR signal in remote regions) and to the anatomical complexity of chest wall boundary (Fig. 2). (Figure Presented) Given its accuracy and speed, our breast segmentation method appears to be ready for clinical use as a part of larger workflow to generate routine diagnostic reports
EMBASE:622627472
ISSN: 1861-6429
CID: 3179282
Comparison between qualitative and quantitative assessment of background parenchymal enhancement on breast MRI
Pujara, Akshat C; Mikheev, Artem; Rusinek, Henry; Gao, Yiming; Chhor, Chloe; Pysarenko, Kristine; Rallapalli, Harikrishna; Walczyk, Jerzy; Moccaldi, Melanie; Babb, James S; Melsaether, Amy N
BACKGROUND: Potential clinical implications of the level of background parenchymal enhancement (BPE) on breast MRI are increasing. Currently, BPE is typically evaluated subjectively. Tests of concordance between subjective BPE assessment and computer-assisted quantified BPE have not been reported. PURPOSE OR HYPOTHESIS: To compare subjective radiologist assessment of BPE with objective quantified parenchymal enhancement (QPE). STUDY TYPE: Cross-sectional observational study. POPULATION: Between 7/24/2015 and 11/27/2015, 104 sequential patients (ages 23 - 81 years, mean 49 years) without breast cancer underwent breast MRI and were included in this study. FIELD STRENGTH/SEQUENCE: 3T; fat suppressed axial T2, axial T1, and axial fat suppressed T1 before and after intravenous contrast. ASSESSMENT: Four breast imagers graded BPE at 90 and 180 s after contrast injection on a 4-point scale (a-d). Fibroglandular tissue masks were generated using a phantom-validated segmentation algorithm, and were co-registered to pre- and postcontrast fat suppressed images to define the region of interest. QPE was calculated. STATISTICAL TESTS: Receiver operating characteristic (ROC) analyses and kappa coefficients (k) were used to compare subjective BPE with QPE. RESULTS: ROC analyses indicated that subjective BPE at 90 s was best predicted by quantified QPE =20.2 = a, 20.3-25.2 = b, 25.3-50.0 = c, >50.0 = d, and at 180 s by quantified QPE = 32.2 = a, 32.3-38.3 = b, 38.4-74.5 = c, >74.5 = d. Agreement between subjective BPE and QPE was slight to fair at 90 s (k = 0.20-0.36) and 180 s (k = 0.19-0.28). At higher levels of QPE, agreement between subjective BPE and QPE significantly decreased for all four radiologists at 90 s (P = 0.004) and for three of four radiologists at 180 s (P = 0.004). DATA CONCLUSION: Radiologists were less consistent with QPE as QPE increased. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017.
PMID: 29140576
ISSN: 1522-2586
CID: 2785262
Basal forebrain septal nuclei are enlarged in healthy subjects prior to the development of Alzheimer's disease
Butler, Tracy; Harvey, Patrick; Deshpande, Anup; Tanzi, Emily; Li, Yi; Tsui, Wai; Silver, Caroline; Fischer, Esther; Wang, Xiuyuan; Chen, Jingyun; Rusinek, Henry; Pirraglia, Elizabeth; Osorio, Ricardo S; Glodzik, Lidia; de Leon, Mony J
Alzheimer's disease (AD) is known to be associated with loss of cholinergic neurons in the nucleus basalis of Meynert, located in the posterior basal forebrain. Structural changes of septal nuclei, located in the anterior basal forebrain, have not been well studied in AD. Using a validated algorithm, we manually traced septal nuclei on high-resolution coronal magnetic resonance imaging (MRI) in 40 subjects with mild cognitive impairment (MCI) or AD, 89 healthy controls, and 18 subjects who were cognitively normal at the time of MRI but went on to develop AD an average of 2.8Â years later. We found that cognitively normal subjects destined to develop AD in the future had enlarged septal nuclei as compared to both healthy controls and patients with current MCI or AD. To our knowledge, this is the first time a brain structure has been found to be enlarged in association with risk of AD. Further research is needed to determine if septal enlargement reflects neuroplastic compensation, amyloid deposition, inflammation, or another process and to determine whether it can serve as an early MRI biomarker of AD.
PMID: 29499501
ISSN: 1558-1497
CID: 2966052
Reply: Cerebrospinal Fluid, Hyposmia and Dementia in Alzheimer Disease: Insights from Dynamic PET and a Hypothesis
de Leon, Mony J; Li, Yi; Rusinek, Henry
PMID: 29439014
ISSN: 1535-5667
CID: 2958272
Reply
Thakur, S K; Serulle, Y; Miskin, N P; Rusinek, H; Golomb, J; George, A E
PMID: 29269401
ISSN: 1936-959x
CID: 2905902
The nonlinear relationship between cerebrospinal fluid Aβ42 and tau in preclinical Alzheimer's disease
de Leon, Mony J; Pirraglia, Elizabeth; Osorio, Ricardo S; Glodzik, Lidia; Saint-Louis, Les; Kim, Hee-Jin; Fortea, Juan; Fossati, Silvia; Laska, Eugene; Siegel, Carole; Butler, Tracy; Li, Yi; Rusinek, Henry; Zetterberg, Henrik; Blennow, Kaj
Cerebrospinal fluid (CSF) studies consistently show that CSF levels of amyloid-beta 1-42 (Aβ42) are reduced and tau levels increased prior to the onset of cognitive decline related to Alzheimer's disease (AD). However, the preclinical prediction accuracy for low CSF Aβ42 levels, a surrogate for brain Aβ42 deposits, is not high. Moreover, the pathology data suggests a course initiated by tauopathy contradicting the contemporary clinical view of an Aβ initiated cascade. CSF Aβ42 and tau data from 3 normal aging cohorts (45-90 years) were combined to test both cross-sectional (n = 766) and longitudinal (n = 651) hypotheses: 1) that the relationship between CSF levels of Aβ42 and tau are not linear over the adult life-span; and 2) that non-linear models improve the prediction of cognitive decline. Supporting the hypotheses, the results showed that a u-shaped quadratic fit (Aβ2) best describes the relationship for CSF Aβ42 with CSF tau levels. Furthermore we found that the relationship between Aβ42 and tau changes with age-between 45 and 70 years there is a positive linear association, whereas between 71 and 90 years there is a negative linear association between Aβ42 and tau. The quadratic effect appears to be unique to Aβ42, as Aβ38 and Aβ40 showed only positive linear relationships with age and CSF tau. Importantly, we observed the prediction of cognitive decline was improved by considering both high and low levels of Aβ42. Overall, these data suggest an earlier preclinical stage than currently appreciated, marked by CSF elevations in tau and accompanied by either elevations or reductions in Aβ42. Future studies are needed to examine potential mechanisms such as failing CSF clearance as a common factor elevating CSF Aβxx analyte levels prior to Aβ42 deposition in brain.
PMCID:5802432
PMID: 29415068
ISSN: 1932-6203
CID: 2947732
3D Registration of mpMRI for Assessment of Prostate Cancer Focal Therapy
Orczyk, Clement; Rosenkrantz, Andrew B; Mikheev, Artem; Villers, Arnauld; Bernaudin, Myriam; Taneja, Samir S; Valable, Samuel; Rusinek, Henry
RATIONALE AND OBJECTIVES: This study aimed to assess a novel method of three-dimensional (3D) co-registration of prostate magnetic resonance imaging (MRI) examinations performed before and after prostate cancer focal therapy. MATERIALS AND METHODS: We developed a software platform for automatic 3D deformable co-registration of prostate MRI at different time points and applied this method to 10 patients who underwent focal ablative therapy. MRI examinations were performed preoperatively, as well as 1 week and 6 months post treatment. Rigid registration served as reference for assessing co-registration accuracy and precision. RESULTS: Segmentation of preoperative and postoperative prostate revealed a significant postoperative volume decrease of the gland that averaged 6.49 cc (P = .017). Applying deformable transformation based on mutual information from 120 pairs of MRI slices, we refined by 2.9 mm (max. 6.25 mm) the alignment of the ablation zone, segmented from contrast-enhanced images on the 1-week postoperative examination, to the 6-month postoperative T2-weighted images. This represented a 500% improvement over the rigid approach (P = .001), corrected by volume. The dissimilarity by Dice index of the mapped ablation zone using deformable transformation vs rigid control was significantly (P = .04) higher at the ablation site than in the whole gland. CONCLUSIONS: Our findings illustrate our method's ability to correct for deformation at the ablation site. The preliminary analysis suggests that deformable transformation computed from mutual information of preoperative and follow-up MRI is accurate in co-registration of MRI examinations performed before and after focal therapy. The ability to localize the previously ablated tissue in 3D space may improve targeting for image-guided follow-up biopsy within focal therapy protocols.
PMCID:6025844
PMID: 29122471
ISSN: 1878-4046
CID: 2772952