Pattern Of Amyloid Deposition Research Articles

Morphological findings in different subtypes of hepatic amyloid

The classic findings have been well described for light-chain amyloid involving the liver. In addition to light chain, however, many additional proteins are now known to be amyloidogenic and can involve the liver. A total of 58 surgical pathology specimens with amyloid deposits were analyzed for patterns of amyloid deposition, including amyloid from light chain lambda (N = 17), light chain kappa (N = 15), transthyretin (N = 15), serum amyloid A (N = 4), apolipoprotein A1 (N = 4), fibrinogen alpha (N = 2), LECT2 (N = 1). Amyloid deposits predominately targeted the liver vasculature, including the walls of the hepatic arteries, portal veins, and sinusoids. While there was overlap, light chain amyloid predominately involved the sinusoids, while transthyretin amyloid predominately targeted the hepatic arteries, especially the larger ones in the hilum and larger portal tracts. Serum amyloid A formed nodular deposits that started in the portal vasculature but then extended into the portal tract stroma, leading to large, bulbous, portal-based amyloid deposits. Apolipoprotein A amyloid also formed large portal-based nodules. Fibrinogen was mild and subtle on H&E and predominately affected portal veins. Amyloid deposits in hilar nerves were prominent with amyloid light chain, transthyretin, and apolipoprotein A1. In conclusion, the histology of hepatic amyloid is diverse and shows several distinct clusters of findings that can aide in recognition in surgical pathology specimens.

Brain structural indicators of β-amyloid neuropathology

Recent efforts demonstrated the efficacy of identifying early-stage neuropathology of Alzheimer’s disease (AD) through lumbar puncture cerebrospinal fluid assessment and positron emission tomography (PET) radiotracer imaging. These methods are effective yet are invasive, expensive, and not widely accessible. We extend and improve the multiscale structural mapping (MSSM) procedure to develop structural indicators of β-amyloid neuropathology in preclinical AD, by capturing both macrostructural and microstructural properties throughout the cerebral cortex using a structural MRI. We find that the MSSM signal is regionally altered in clear positive and negative cases of preclinical amyloid pathology (N = 220) when cortical thickness alone or hippocampal volume is not. It exhibits widespread effects of amyloid positivity across the posterior temporal, parietal, and medial prefrontal cortex, surprisingly consistent with the typical pattern of amyloid deposition. The MSSM signal is significantly correlated with amyloid PET in almost half of the cortex, much of which overlaps with regions where beta-amyloid accumulates, suggesting it could provide a regional brain ‘map’ that is not available from systemic markers such as plasma markers.

Prospects of imaging retinal amyloid beta using fluorescent probes for early diagnosis of Alzheimers disease

Alzheimers Disease is the most common cause of dementia amongst older adults, affecting more than 55 million people globally. Identifying accessibility concerns for conventional methods used for diagnostics, this review focuses on an alternative approach detecting amyloid beta in the retina. The utility of this biomarker is yet to be verified due to the low number of in vivo studies in AD patients, as well as the need for further investigation on the subtle differences between cerebral and retinal patterns of amyloid deposition. However, this approach has shown great promise as recent in vivo studies of larger sample sizes are conducted. Exemplifying the applications of curcumin, this paper also examines current methodologies in rA research and evaluates the outlook of chemically modifying fluorescent probes for oligomeric selectivity.

Deep Learning patterns of Aβ accumulation in Alzheimer’s Disease

AbstractBackgroundAccumulation of amyloid (Aß) plaques is an early pathologic change of Alzheimer’s Disease (AD). However, the mechanisms and pathways by which amyloid spreads across the cerebrum are not fully understood. Deriving distinct dimensions of amyloid deposition and their associations with biomedical factors could be useful to understand how amyloid propagates. In this analysis, we identified two distinct subtypes of progression based on spatiotemporal variations using a recently developed data‐driven, deep learning clustering method called Surreal‐GAN1.MethodWe used data from 482 A+ and 801 A‐ subjects with 18F‐florbetapir PET from the Alzheimer’s Disease Neuroimaging Initiative (ADNI; N = 832) and 11C‐PiB from the Preclinical AD consortium (PAC; N = 451). Standardized uptake value ratio (SUVR) maps (cerebellar GM reference) were transformed to reference space. We derived amyloid status using Gaussian mixture modelling of mean total cortical SUVR for each of 4 sites. We then applied non‐negative matrix factorization2 on the SUVR maps to identify data‐driven common patterns of deposition across the sample. Next, we applied Surreal‐GAN on a total of 1283 subjects to determine the amyloid spatiotemporal subtypes. Correlations with clinical and cognitive variables were evaluated.ResultsParticipants were 30%/22% female and had mean age 74.9 (±7.4)/ 67.9(±9.1) years for ADNI and PAC, respectively. We identified 24 components from NMF (Fig 1A) after excluding 6 as non‐target features. Surreal‐GAN showed optimal agreement indices for two patterns. While both patterns shared involvement of posterior cingulate/precuneus and inferior frontal cortex, pattern r1 shows relatively more occipital deposition and pattern r2 shows more frontal deposition (Fig 1B), as seen when comparing strongly r1 vs strongly r2 participants using voxel‐based morphometry (Fig 2). Both were associated with worse global cognitive function and worsening neurodegeneration (Table 1). r1 correlates with white matter hyperintensity volume, a measure of cerebrovascular disease, while pattern r2 is associated with the presence of APOE e4 alleles.ConclusionEmploying a data‐driven deep learning‐based approach, we derived more than one dissociable pattern of amyloid deposition, potentially differently influenced by vascular disease (r1/occipital) and genetics (r1/frontal). These findings could inform identification of subgroups of individuals who may or may not be responsive to particular clinical intervention.

Deciphering the clinico-radiological heterogeneity of dysexecutive Alzheimer's disease.

Dysexecutive Alzheimer's disease (dAD) manifests as a progressive dysexecutive syndrome without prominent behavioral features, and previous studies suggest clinico-radiological heterogeneity within this syndrome. We uncovered this heterogeneity using unsupervised machine learning in 52 dAD patients with multimodal imaging and cognitive data. A spectral decomposition of covariance between FDG-PET images yielded six latent factors ("eigenbrains") accounting for 48% of variance in patterns of hypometabolism. These eigenbrains differentially related to age at onset, clinical severity, and cognitive performance. A hierarchical clustering on the eigenvalues of these eigenbrains yielded four dAD subtypes, i.e. "left-dominant," "right-dominant," "bi-parietal-dominant," and "heteromodal-diffuse." Patterns of FDG-PET hypometabolism overlapped with those of tau-PET distribution and MRI neurodegeneration for each subtype, whereas patterns of amyloid deposition were similar across subtypes. Subtypes differed in age at onset and clinical severity where the heteromodal-diffuse exhibited a worse clinical picture, and the bi-parietal had a milder clinical presentation. We propose a conceptual framework of executive components based on the clinico-radiological associations observed in dAD. We demonstrate that patients with dAD, despite sharing core clinical features, are diagnosed with variability in their clinical and neuroimaging profiles. Our findings support the use of data-driven approaches to delineate brain-behavior relationships relevant to clinical practice and disease physiology.

Deciphering the clinico‐radiological heterogeneity of dysexecutive Alzheimer’s disease using unsupervised machine learning techniques

AbstractBackgroundDysexecutive Alzheimer's disease (dAD) is a relatively early‐onset variant of AD primarily degrading core executive functions in the absence of predominant behavioral symptoms. Clinical observations suggest substantial variability in clinical, cognitive and neuroimaging profiles within this syndrome. In this presentation, we will discuss our ongoing work disentangling this heterogeneity using unsupervised machine learning techniques.MethodWe collected clinical, neuropsychological and multimodal imaging (MRI, FDG‐PET, amyloid‐PET, tau‐PET) data on 52 dAD patients assessed in our behavioral neurology clinic at Mayo Clinic Rochester. We first performed a spectral clustering analysis based on FDG‐PET to delineate latent patterns of network degeneration (referred as “eigenbrains”) and assessed the relationships between these eigenbrains and clinical and cognitive symptomatology. We then performed a hierarchical clustering on these eigenbrains to derive data‐driven subtypes of dAD. We compared clinical and cognitive data between subtypes, and then compared the imaging profiles to 52 amyloid‐negative age‐ and sex‐matched controls.ResultSix eigenbrains explained approximatively 48% of the variance in FDG‐PET patterns and primarily reflected heteromodal to primary motor/sensory, left‐right hemispheric asymmetry, and anterior‐to‐posterior gradients of macro‐scale cortical organization (Fig 1). These eigenbrains differentially related to reported age at symptom onset, degree of clinical impairment, and performance on a wide range of cognitive domains (executive functions, episodic memory, and visuospatial). Hierarchical clustering revealed four dAD subtypes (diffuse, biparietal, left‐hemisphere, right‐hemisphere). These subtypes differed in reported age at symptom onset and cognitive profile, where the heteromodal‐diffuse subtype exhibited an overall worse clinical picture and the biparietal had a milder profile compared to other subtypes, which was not explained by disease duration. Additionally, spatial patterns of tau distribution and neurodegeneration overlapped with patterns of FDG‐PET hypometabolism in each subtype, whereas patterns of amyloid deposition were similar across subtypes (Figs 2 & 3).ConclusionAlmost half of the variance in macro‐scale patterns of hypometabolism in this dAD cohort was accounted for by six eigenbrains. These eigenbrains captured the inter‐individual variability in age at symptom onset and cognitive impairment. Four dAD subtypes derived from these eigenbrains revealed meaningful differences in clinical, cognitive, and imaging profiles. Recognizing this heterogeneity has significant clinical implications for diagnosis, prognosis, and symptom monitoring.

Topographic Distribution Pattern in Hepatic Amyloidosis Presenting with Portal Hypertension

The liver is often involved in both primary and secondary forms of amyloidosis. Significant clinical evidence of portal hypertension is relatively uncommon and seems to be related to the reduced sinusoidal lumen and increased resistance to blood flow due to massive perisinusoidal amyloid deposits. The relationships between the pattern and extent of amyloid deposition in patients presenting with portal hypertension have not yet been clearly demonstrated. This study is focusing on the topographic distribution of amyloidosis in patients presenting with portal hypertension. The study included biopsy-proven cases of hepatic amyloidosis. The clinical, biochemical, and serological data, involvement of the extrahepatic organs, and HVPG values were recorded. Tissue sections were re-evaluated for the distribution patterns of amyloid deposits. We had 41 patients with hepatic amyloidosis, of which, 32 were male. A mixed pattern (sinusoidal and vascular) was the most common (32/41; 78%). Hepatic venous pressure gradient was available in 21 cases. Portal hypertension was found in 14 patients (14/21; 67%). Cases of portal hypertension were found to have a sinusoidal pattern (3/14; 21.4%), vascular pattern (1/14; 7.1%), or a mixed sinusoidal and vascular pattern (10/14; 71.4%). Those not having portal hypertension showed hepatic artery (HA) involvement in 6/7 (85.7%) cases. A comparative analysis between portal hypertension (PTH) and non-PTH groups showed that HA amyloid deposition was dominant in the non-PTH group (6/7; 85.7%) and sinusoidal deposition in the PTH group (13/14; 92.8%). The difference was found to be significant (P<0.05). We found that portal hypertension was noted in cases with diffuse sinusoidal deposition or mixed sinusoidal with portal vein deposition. In the non-PHT group, the deposition was mainly in HA alone.

Prognostic value of histopathological scoring and grading in patients with renal AA amyloidosis.

The amount and distribution pattern of amyloid deposits may contribute to renal function and outcome, given the great diversity of renal involvement in amyloidosis. The aim of this study was to analyze the impact of histological characteristics of patients with biopsy-proven renal AA amyloidosis (AAA)on renal outcome. Renal biopsies of 37 patients with AAA were re-evaluated. The distribution pattern of glomerular amyloid (GA) deposits was classified, the extent of amyloid deposits in glomeruli, vessel, and interstitium and other histopathologic lesions were scored, and renal amyloid prognostic score (RAPS) was determined by summing all scores. Their potential prognostic relevance on renal outcome was investigated. GA and vascular amyloid (VA) deposits were noted in all cases, interstitial amyloid (IA) was detected in 70.2%. GA deposits were predominantly seen in diffuse mesengiocapillary fashions (class IV) (51.4%). GA class, the extent of GA, VA, IA deposit, and RAPS, as well as interstitial fibrosis (IF) and interstitial inflammation were correlated to renal function at diagnosis. During the median follow-up of 52months, 13 patients developed doubling of serum creatinine or end stage renal disease and they had a higher degree of GA and VA load (p = 0.03 and p = 0.042, respectively) as compared to the remaining patients. VA load, but not GA and RAPS grade, was associated with poor renal outcome (HR 3.016, 95% CI 1.45-6.25, p = 0.003). Baseline renal function is closely linked to the extent of AA amyloid deposit in renal parenchyma but only VA load was a predictor of renal outcome in AAA patients.

Prominent Striatum Amyloid Retention in Early-Onset Familial Alzheimer's Disease With PSEN1 Mutations: A Pilot PET/MR Study.

Background: With the advancements of amyloid imaging in recent years, this new imaging diagnostic method has aroused great interest from researchers. Till now, little is known regarding amyloid deposition specialty in patients with early-onset familial Alzheimer's disease (EOFAD), and even less is known about its role in cognitive impairments.Objectives: Our study aimed to evaluate the amyloid deposition in five patients with EOFAD, 15 patients with late-onset sporadic AD, and 12 healthy subjects utilizing 11C-labeled Pittsburgh compound-B (11C-PiB) amyloid PET imaging. Moreover, we figured out the correlation between striatal and cortical standardized uptake value ratios (SUVRs). We also investigated the correlation between 11C-PiB retention and cognitive presentation.Results: All patients with EOFAD showed high amyloid deposition in the striatum, a pattern that is not usually seen in patients with late-onset sporadic AD. The SUVR in the striatum, especially in the amygdala, showed significant correlations with cortex SUVR in EOFAD. However, neither striatal nor cortical 11C-PiB retention was related to cognitive decline.Conclusions: The amyloid distribution in patients with EOFAD differs from late-onset sporadic AD, with higher amyloid deposits in the striatum. Our study also demonstrated positive correlations in 11C-PiB retention between the striatum and other cortical areas. We revealed that the distribution of amyloid in the brain is not random but diffuses following the functional and anatomical connections. However, the degree and pattern of amyloid deposition were not correlated with cognitive deficits.

Asymmetric Amyloid Deposition as an Early Sign of Progression in Mild Cognitive Impairment Due to Alzheimer Disease.

In typical Alzheimer disease with dementia (ADD), amyloid pathologies affect both cerebral hemispheres symmetrically. However, the spatial distribution of amyloid-β (Aβ) in the early stage of ADD or over the course of disease has not been investigated. Therefore, we explored asymmetric pattern of Aβ deposition in both hemispheres according to the ADD continuum using 18F-florbetaben PET. Sixty-eight subjects, including 15 Aβ-negative normal controls, 28 Aβ-positive mild cognitive impairment (Aβ+ MCI), and 25 Aβ-positive ADD (Aβ+ ADD) subjects, were enrolled. Differences in the asymmetry index and SUV ratio in each of the 6 target regions (4 cortical lobes, cingulate, precuneus) plus composite region between groups were explored. The composite and target regional asymmetry indices were significantly different between groups and was highest in Aβ+ MCI (composite, occipital, and temporal, P < 0.001; frontal, P = 0.004). The composite and target regional SUV ratios were significantly different according to 3 groups with gradual increase and were highest in Aβ+ ADD (composite and all target regions, P < 0.001). The asymmetric pattern of amyloid deposition was distinct between Aβ-negative normal controls and Aβ+ MCI. This pattern disappeared as the disease progressed. These data indicate that asymmetric amyloid deposition may be an early sign of MCI over the course of ADD.

Abstract P367: Brain-Wide Quantification of Amyloid in Transgenic Mice Using Volumetric Imaging and Automated Image Analysis

Localizing and quantifying amyloid in three dimensions furthers understanding of spatial patterns of amyloid deposition and disease progression in experimental models of cerebral amyloid angiopathy (CAA). Serial two-photon tomography (STPT) is ideal for this purpose because it produces 3D datasets of the whole mouse brain in a matter of hours. We present an optimized pipeline for fluorescent whole-brain labeling of amyloid and vasculature, STPT imaging of labeled brains, machine learning-aided classification of vascular and parenchymal amyloid, registration of images to a standard reference atlas, and automated quantification of these signals across brain regions. We used traditional histological sectioning and slide mounted imaging to compare and optimize published methods of fluorescent amyloid and vascular labeling. An intraperitoneal injection of methoxy-X04 delivered the day before euthanasia was chosen to label amyloid. Cerebral vessels are visualized by transcardial perfusion of rhodamine-B isothiocyanate in gelatin. Labeled brains are imaged by STPT and rendered in 3D to appreciate regional amyloid distribution. Volumetric image datasets are quantified using a modification of our custom image analysis pipeline. Pixels are classified as vascular or parenchymal amyloid with supervised machine learning methods. Classified signals are registered into the Allen Institute for Brain Science Common Coordinate Framework version 3.0 for quantification. This strategy produces high resolution volumetric images amenable to automatic quantification of parenchymal and vascular amyloid deposits throughout the brain, appropriate for studies involving large numbers of experimental brains in rodent models of CAA. Figure 1: A 3D rendering of prediction probability maps of a whole labelled mouse brain depicting fluorescent signals that were automatically classified as parenchymal amyloid (cyan), vascular amyloid (yellow) and brain parenchyma.

Spatial Patterns of Amyloid Deposition in Patients with Chronic Focal or Diffuse Traumatic Brain Injury Using 18F-FPYBF-2 PET.

AimAmyloid-β (Aβ) accumulation, accelerated by traumatic brain injury (TBI), may play a crucial role in neurodegeneration in chronic-stage TBI. The injury type could influence Aβ dynamics because of TBI’s complex, heterogeneous nature. We, therefore, investigated spatial patterns of amyloid deposition according to injury type after TBI using 5-(5-(2-(2-(2-[F]-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N-methylpyridin-2-amine (18F-FPYBF-2) positron emission tomography (PET).MethodsAltogether, 20 patients with chronic TBI [12 with focal injury, 8 with diffuse axonal injury (DAI)] underwent 18F-FPYBF-2 PET, structural magnetic resonance imaging (MRI), and neuropsychological examination. Additionally, 50 healthy controls underwent either 18F-FPYBF-2 PET (n=30) or structural MRI (n=20).ResultsStandardized uptake value ratio (SUVR) on PET images and regional brain volumes were measured in four cortical (frontal, parietal, occipital, temporal) and subcortical (combined caudate, putamen, pallidum, thalamus) regions. Patients with DAI showed significantly increased (compared with controls) SUVR in occipital and temporal cortices and decreased brain volume in occipital cortex (corrected p < 0.05). Although patients with focal injury showed decreased SUVR in all regions except occipital cortex, there were no significant differences (compared with controls) in the SUVR in any regions. There were no significant correlations between increased SUVR and neuropsychological impairments in patients with DAI.ConclusionVarying spatial patterns of amyloid deposition suggest amyloid pathology diversity depending on the injury type in chronic-TBI patients.

Associations Between the Immunoglobulin Germline Gene Usage and the Tropism of Organ Involvement and Renal Amyloid Deposition Patterns in Immunoglobulin Light-Chain Amyloidosis by Mass Spectrometry

Associations Between the Immunoglobulin Germline Gene Usage and the Tropism of Organ Involvement and Renal Amyloid Deposition Patterns in Immunoglobulin Light-Chain Amyloidosis by Mass Spectrometry

Comparison of Amyloid Positivity Rate and Accumulation Pattern between Amnestic and Non-Amnestic Type Mild Cognitive Impairment.

ObjectiveWe aimed to compare cerebral beta-amyloid protein (Aβ) positivity rate and amyloid accumulation pattern on amyloid positron emission tomography (PET) between mild cognitive impairment (MCI) subtypes, i.e. amnestic mild cognitive impairment (aMCI) and non-amnestic mild cognitive impairment (naMCI). MethodsThe study participants were 34 naMCI patients and age-, sex- and education-matched 68 aMCI patients (1:2 ratio) who visited the Dementia and Age-Associated Cognitive Decline Clinic of the Seoul National University Hospital. All participants received comprehensive clinical and neuropsychological assessments and [18F] florbetaben PET. ResultsAβ positivity rate of naMCI group (26.5%) was significantly lower than that of aMCI group (64.7%). Among Aβ positive individuals, there was no difference in Aβ accumulation pattern between naMCI and aMCI. ConclusionThe findings suggest that MCI subtypes based on impaired cognitive domains have a differential association with brain Aβ deposition, a core pathology of AD. Amnestic subtype of MCI are more closely associated with cerebral Aβ deposition compared to non-amnestic subtype. In contrast, the pattern of amyloid deposition does not appear to have any difference between the subtypes.

P0423CLINICOPATHOLOGICAL STUDY OF RENAL AMYLOIDOSIS

Abstract Background and Aims Amyloidosis constitute a heterogenous group of disorders characterized by extracellular deposition of abnormally folded proteins in different tissues and organs leading to organ dysfunction. An emphasis has been made to classify, grade and score the amyloid deposits in different renal compartments and correlate them with the clinical features, type of amyloid and outcome. Method The study included all renal biopsies done in department of nephrology diagnosed as amyloidosis in association with Department of Pathology, SGPGIMS from January 2009 to December 2018 and retrospectively analysed. Besides biochemical parameters ,serum and urine electrophoresis ,immunofixation ,bone biopsy ,FNAC and kidney biopsy was done for the diagnosis. Results One hundred forty seven (147) renal biopsies diagnosed as Amyloidosis at the Department of Pathology, SGPGIMS, Lucknow from January 2009 and December 2018 .The mean age was 51.33 ± 14.50 years (Median: 52 year), most common age group affected with Renal Amyloidosis was 50-60 years(6 th decade) in males, while it was one decade younger in females (40-50years). Multiple myeloma as the primary disease was present in 18/147 (12.2%). History of chronic inflammatory disease was found in 65 patients (44%). Tuberculosis was the most common infection while rheumatoid arthritis (18.5%) was found to be the second most commonly associated chronic inflammatory condition. Mean serum creatinine was 2.04 ±1.72 mg/dl. Peripheral neuropathy and bleeding episodes were rarely seen (&amp;lt;5%). Nephrotic range proteinuria was found in 78% Only eight out of eighteen patients with Multiple myeloma showed reversal of A:G ratio. M-band was present in 34 patients . Lambda light chain was found more commonly associated with renal amyloidosis. Out of 71, 27 aspiration cytology smears revealed congophilic deposits which showed apple green birefringence on polarizing microscopy. Bone marrow biopsy was performed in 76, among them 17 patients showed &amp;gt; 10% plasma cells. Histology commonly seen was diffuse mesangio capillary in 77%, followed by advanced amyloidosis (20%). Most of the renal biopsies (84%) showed amyloid deposition in &amp;gt;50% area of glomeruli. Most of the renal biopsies (41.5%) showed mild tubular atrophy. Renal amyloid prognostic score (RAPS) was calculated combining all scores in different renal compartments revealed 74% patients belonged to Grade III. Immuno histochemistry for typing of renal amyloid revealed SAA in 61, two cases were placed in a different group, termed as dual AL+AA positive. one case with positive ALect2 deposits in renal biopsy. Survival analysis showed showed that AL had poor overall survival as compared to AA typePatients with high serum creatinine value (&amp;gt;2.0 mg/dl) had poor survival as compared to the patients with serum creatinine &amp;lt;2.0mg/dl. significant poor survival in patients withcardiomyopathy (p value=0.004) and hypotension (p value=0.026). High burden of plasma cells (&amp;gt; 10%) in bone marrow aspirate also showed significant poor survival. Conclusion Final typing of amyloid deposits in kidney biopsy with clinicopathological evaluation revealed AA was the predominant subtype comprising of 50% (n=73) of renal amyloidosis. AL was 33% (n=48) of all cases. The different class of pattern of amyloid deposition correlated well with the grade of amyloid deposition in renal biopsy. Poor survival outcomes are evident with patients with hypotension ,cardiomyopathy, higher grades of amyloid on histology, serum creatinine &amp;gt; 2 mg% and high burden of plasma cells (&amp;gt;10%) in bone marrow aspirate. Thus the number of patients with cardiomyopathy, hypotension and &amp;gt; 10% plasma cells in bone marrow aspirate performed poorly however the study is smalland needs to be validated on a larger cohort.

Visual and Quantitative Evaluation of Amyloid Brain PET Image Synthesis with Generative Adversarial Network

Conventional data augmentation (DA) techniques, which have been used to improve the performance of predictive models with a lack of balanced training data sets, entail an effort to define the proper repeating operation (e.g., rotation and mirroring) according to the target class distribution. Although DA using generative adversarial network (GAN) has the potential to overcome the disadvantages of conventional DA, there are not enough cases where this technique has been applied to medical images, and in particular, not enough cases where quantitative evaluation was used to determine whether the generated images had enough realism and diversity to be used for DA. In this study, we synthesized 18F-Florbetaben (FBB) images using CGAN. The generated images were evaluated using various measures, and we presented the state of the images and the similarity value of quantitative measurement that can be expected to successfully augment data from generated images for DA. The method includes (1) conditional WGAN-GP to learn the axial image distribution extracted from pre-processed 3D FBB images, (2) pre-trained DenseNet121 and model-agnostic metrics for visual and quantitative measurements of generated image distribution, and (3) a machine learning model for observing improvement in generalization performance by generated dataset. The Visual Turing test showed similarity in the descriptions of typical patterns of amyloid deposition for each of the generated images. However, differences in similarity and classification performance per axial level were observed, which did not agree with the visual evaluation. Experimental results demonstrated that quantitative measurements were able to detect the similarity between two distributions and observe mode collapse better than the Visual Turing test and t-SNE.

Histological grading of hepatic amyloidosis in ducks

Duck farming is very popular in various parts of the world. Even though ducks are highly predisposed to amyloidosis, study on histological grading of amyloidosis and its correlation with gross findings in the visceral organs are scarce. In the current study, we necropsied 112 duck carcasses over a period of one year and the occurrence of hepatic amyloidosis was studied and histological scoring was made. The study revealed amyloidosis in 61.61 per cent carcasses. We analysed the livers of such ducks histologically for the extent and pattern of amyloid deposits. The extent of amyloid deposition was graded as mild, moderate or severe. In severe amyloidosis without cellularity, the liver grossly showed deep yellow discolouration of the parenchyma. In moderate amyloidosis characterised by islands of hepatocytes and erythrocytes, the liver grossly showed pale pink to brownish discolouration. In mild amyloidosis with preserved hepatocellular architecture, the gross discolouration of the liver was minimum. The histological severity of amyloidosis could be directly correlated with the gross features in liver tissue specimens.

Brain areas with normatively greater cerebral perfusion in early life may be more susceptible to beta amyloid deposition in late life.

Background:The amyloid cascade hypothesis characterizes the stereotyped progression of pathological changes in Alzheimer’s disease (AD) beginning with beta amyloid deposition, but does not address the reasons for amyloid deposition. Brain areas with relatively higher neuronal activity, metabolic demand, and production of reactive oxygen species in earlier life may have higher beta amyloid deposition in later life. The aim of this study was to investigate early life patterns of perfusion and late life patterns of amyloid deposition to determine the extent to which normative cerebral perfusion predisposes specific regions to future beta amyloid deposition.Materials and Methods:One hundred twenty-eight healthy, older human subjects (age: 56–87 years old; 44% women) underwent positron emission tomography (PET) imaging with [11C]PiB for measures of amyloid burden. Cerebral perfusion maps derived from 47 healthy younger adults (age: 22–49; 47%) who had undergone single photon emission computed tomography (SPECT) imaging, were averaged to create a normative template, representative of young, healthy adults. Perfusion and amyloid measures were investigated in 31 cortical regions from the Hammers atlas. We examined the spatial relationship between normative perfusion patterns and amyloid pathophysiology.Results:The pattern of increasing perfusion (temporal lobe < parietal lobe < frontal lobe < insula/cingulate gyrus < occipital lobe; F(4,26) = 7.8, p = 0.0003) in young, healthy adults was not exactly identical to but approximated the pattern of increasing amyloid burden (temporal lobe < occipital lobe < frontal lobe < parietal lobe < insula/cingulate gyrus; F(4,26) = 5.0, p = 0.004) in older adults. However, investigating subregions within cortical lobes provided consistent agreement between ranked normative perfusion patterns and expected Thal staging of amyloid progression in AD (Spearman r = 0.39, p = 0.03).Conclusion:Our findings suggest that brain areas with normatively greater perfusion may be more susceptible to amyloid deposition in later life, possibly due to higher metabolic demand, and associated levels of oxidative stress and inflammation.

The Spatial-Temporal Ordering of Amyloid Pathology and Opportunities for PET Imaging.

Although clinical routine focuses on dichotomous and visual interpretation of amyloid PET, regional image assessment in research settings may yield additional opportunities. Understanding the regional-temporal evolution of amyloid pathology may enable earlier identification of subjects in the Alzheimer Disease pathologic continuum, as well as a finer-grained assessment of pathology beyond traditional dichotomous measures. This review summarizes current research in the detection of regional amyloid deposition patterns and its potential for staging amyloid pathology. Pathology studies, cross-sectional and longitudinal PET-only studies, and comparative PET and autopsy studies are included. Despite certain differences, cortical deposition generally precedes striatal pathology, and in PET-only studies, medial cortical regions are seen to accumulate amyloid earlier than lateral regions. Based on regional amyloid PET, multiple studies have developed and implemented models for staging amyloid pathology that could improve subject selection into secondary prevention trials and visual assessment in clinical routine.

Magnetic Resonance Elastography of Liver in Light Chain Amyloidosis.

In this paper, we present our preliminary findings regarding magnetic resonance elastography (MRE) on the livers of 10 patients with systemic amyloidosis. Mean liver stiffness measurements (LSM) and spleen stiffness measurements (SSM) were obtained. Magnetic resonance imaging (MRI) images were analyzed for the distribution pattern of amyloid deposition. Pearson correlation analysis was performed in order to study the correlation between LSM, SSM, liver span, liver volume, spleen span, spleen volume, serum alkaline phosphatase (ALP), N-terminal pro b-type natriuretic peptide (NT pro BNP), and the kappa and lambda free light chains. An increase in mean LSM was seen in all patients. Pearson correlation analysis showed a statistically significant correlation between LSM and liver volume (r = 0.78, p = 0.007) and kappa chain level (r = 0.65, p = 0.04). Interestingly, LSM did not correlate significantly with SSM (r = 0.45, p = 0.18), liver span (r = 0.57, p = 0.08), or serum ALP (r = 0.60, p = 0.07). However, LSM correlated significantly with serum ALP when corrected for liver volume (partial correlation, r = 0.71, p = 0.03) and NT pro BNP levels (partial correlation, r = 0.68, p = 0.04). MRI review revealed that amyloid deposition in the liver can be diffuse, lobar, or focal. MRE is useful for the evaluation of hepatic amyloidosis and shows increased stiffness in hepatic amyloidosis. MRE has the potential to be a non-invasive quantitative imaging marker for hepatic amyloidosis.