Citations

AbstractBackgroundRecent advances in automatic face recognition have increased the risk that de‐identified research imaging data could be re‐identified from face imagery in brain scans.MethodAn ADNI committee of independent imaging experts evaluated 11 published techniques for face‐deidentification (“de‐facing”) and selected four algorithms (FSL‐UK Biobank, HCP/XNAT, mri_reface, and BIC) for formal testing using 183 longitudinal scans of 61 racially and ethnically diverse ADNI participants, evaluated by their facial feature removal on 3D rendered surfaces (confirming sufficient privacy protection) and by comparing measurements from ADNI routine image analyses on unmodified vs. de‐faced images (confirming negligible side effects on analyses).ResultEffects of the de‐facing methods on FreeSurfer at UCSF (Figure 1‐top), ASHS at University of Pennsylvania (Figure 1 bottom‐left), and longitudinal atrophy at Mayo Clinic (Figure 1 bottom‐right) were comparable with each other and sufficiently small vs. unmodified scans to recommend de‐facing in ADNI‐4. The FSL and mri_reface methods were more thorough in removing facial features, partly because these also removed ears (Figure 2‐top). mri_reface was recommended for ADNI‐4 primarily because fewer (zero) images had modified brain (Figure 2‐bottom), and ADNI leadership approved de‐facing with mri_reface. ADNI performed a second validation of its latest version on another diverse sample of 100 ADNI‐3 participants. These analyses included: boundary shift interval at University College London, where average differences in measurements were all <0.05%; cortical white matter hyperintensities at UC Davis, where they found “minimum impact” (R>0.97); and others.ConclusionADNI‐4 de‐faces all indicated image types (Table 1) before subsequent pre‐processing, analyses, and public release. Sites upload images to the central repository (LONI), where they are queued to the MRI Core at Mayo Clinic for de‐facing. Image types requiring de‐facing are de‐faced using mri_reface. Trained analysts inspect de‐faced images to confirm complete removal of the face and complete non‐modification of the brain, and any flagged images are re‐processed manually until issues are resolved. De‐faced images are converted back to DICOM and re‐uploaded for further distribution. Image types not requiring de‐facing are indicated to proceed directly to subsequent steps. In summary, ADNI‐4 has adopted mri_reface because it successfully de‐faces without substantially affecting brain measurements.

Background Immune checkpoint inhibitors (ICIs) are recommended to treat patients with deficient mismatch repair/microsatellite instability high (dMMR/MSI-H) metastatic colorectal cancer (mCRC). Pivotal trials have fixed a maximum ICI duration of 2 years, without a compelling rationale. A shorter treatment duration has the potential to improve patients' quality of life and reduce both toxicity and cost without compromising efficacy. Here we examine whether early treatment discontinuation (ETD) before 13 months in patients without progressive disease (PD) can lead to similar long-term disease control compared with a longer treatment duration (LTD). Methods To assess whether ETD is associated with similar outcomes compared with LTD, we assembled an international cohort of patients with dMMR/MSI-H mCRC treated with ICIs who stopped treatment for a reason other than PD within 395 days (ETD group) and compared them to those who continued for >395 days (LTD group). Outcomes were adjusted for patient/tumor characteristics. Primary endpoint was progression-free survival (PFS) and secondary endpoints were objective response rate (ORR), overall survival (OS) and safety. Results Of 976 patients, 137 and 394 were allocated to the ETD and LTD groups, respectively. In the ETD group, treatment was discontinued due to toxicity (n=56), objective response (n=43), surgery (n=28), patient decision (n=2) or other reasons (n=8). Baseline characteristics were well balanced between the two groups: 22% in both groups received both anti-programmed death-(ligand) 1 (anti-PD-(L)1) + anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4); all others received anti-PD-(L)1 monotherapy. ORR to ICIs was 81% in both groups. Median duration of treatment was ~7 months in the ETD and ~24 months in the LTD group. After a median follow-up of 44 months (IQR: 30–67), similar PFS (HR: 0.92, 95% CI: 0.60 to 1.40, p=0.69) and OS (HR: 1.15, 95% CI: 0.66 to 1.99, p=0.62) from the start of ICIs were observed in ETD and LTD patients. In the ETD group, 28 (20%) patients had a PFS event and 9 restarted ICIs with a disease control rate of 66%. Conclusions In our international series of dMMR/MSI-H mCRC, ETD of ICIs in the absence of PD did not seem detrimental in terms of PFS and OS compared with continuing treatment beyond 1 year. Randomized clinical trials to compare short and long treatment duration are now warranted.

Abstract INTRODUCTION The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is evaluating lifestyle interventions in older adults at risk for cognitive decline and dementia. Here we characterize the baseline data set of the POINTER Imaging ancillary study. METHODS Participants underwent health and cognitive assessments and neuroimaging with multimodal positron emission tomography (PET) (beta‐amyloid [Aβ] and tau) and magnetic resonance imaging (MRI). Framingham risk score (FRS) was used to quantify cardiovascular disease (CVD) risk. RESULTS A total of 1052 participants (31% from underrepresented ethnoracial groups) were enrolled. Compared to Aβ−, Aβ+ (29%) participants were older, had higher apolipoprotein E ( APOE ) ε4 carriage rate and white matter hyperintensity volume, and greater temporal tau. FRS was related to MRI measures, but not AD biomarkers. FRS and tau had independent effects on cognition. DISCUSSION In this heterogenous, at‐risk cohort, CVD risk was related to more abnormal brain structure and poorer cognition, representing a putative non‐AD (Alzheimer's disease) pathway to brain injury and cognitive decline. Highlights The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) cohort is enriched for cardiovascular disease (CVD) and poor lifestyle POINTER Imaging collected multimodal neuroimaging data in this unique, at‐risk cohort Amyloid burden was related to age, apolipoprotein E ( APOE ) ε4 carriage, and measures of disease progression Associations between amyloid and tau, and tau and cognition, were relatively weak CVD risk and tau pathology were independently related to memory

Background: Cardiac rehabilitation (CR) patients demonstrate a high burden of chronic conditions (CC). Both multimorbidity (MM; ≥2 coexisting CC) and aging negatively impact functional capacity, whereas CR improves performance. Age-related difference in cardiorespiratory fitness (CRF, peak oxygen uptake (VO 2 )) in CR patients with MM has not been studied. Hypothesis: We hypothesized improvement in CRF will be attenuated by MM with increasing age in CR patients. Aims: We aimed to identify age-related differences in CRF improvement in CR patients with MM. Methods: Patients ≥18 yrs old who attended ≥1 CR sessions from 1999-2017 and completed cardiopulmonary exercise stress test before and after CR were included. The prevalence of CC was assessed using Rochester Epidemiology Project records-linkage system. Age categories included: Younger (18-49 yrs), Midlife (50-64 yrs) and Older (≥65 yrs). CRF categories included: <0%, 0-8% and >8%. Analysis included Kruskal-Wallis and Chi-squared. Results: Of 622 patients, 75.4% were male. Mean age: 62.9±11.2 yrs; Younger (n=70) age: 42.7±6.8 yrs, 67.1% male; Midlife (n=283) age: 58.3±4.3 yrs, 78.8% male; Older (n=269) age: 73.0±5.2 yrs, 74.0% male. BMI was 29.9±5.4 kg/m 2 (Younger: 30.0±6.7, Midlife: 30.4±5.6, Older: 29.3±4.7; p<.05). Median (Q1, Q3) no. of CR sessions attended was 33(22, 35), with lower attendance in the Younger group: 25(16,34) vs Midlife: 33(20,35) and Older: 34 (29,35), p<.05. Overall, percent change in peak VO 2 was 11.5±21.6% (Younger: 18.8±22.8%, Midlife: 11.6±19.5%, Older: 9.4±23.1%; p<.01). The median number of CC was 7(5,8) with significant differences across groups: Younger: 5(3,7), Midlife: 6(5,8), Older: 7(6,9), p<.01. Number of CC increased with age across all CRF categories (p<.01, Fig. 1). However, there was no difference in number of CC within age groups across categories of CRF, Table 1. Conclusions: Our results suggest that MM increases with age in patients attending CR; however, within a given age group, improvement in CRF does not appear dependent on MM. The impact of age appears to have a greater impact than MM on CRF improvement. Individualized treatment plans should focus on the impact of age-related disparities on CRF improvement among CR patients with MM.

Abstract White matter hyperintensities (WMH) and infarcts found on magnetic resonance imaging (MR infarcts) are common biomarkers of cerebrovascular disease. In this review, we summarize the methods, publications, and conclusions stemming from the Alzheimer's Disease Neuroimaging Initiative (ADNI) related to these measures. We combine analysis of WMH and MR infarct data from across the three main ADNI cohorts with a review of existing literature discussing new methodologies and scientific findings derived from these data. Although ADNI inclusion criteria were designed to minimize vascular risk factors and disease, data across all the ADNI cohorts found consistent trends of increasing WMH volumes associated with advancing age, female sex, and cognitive impairment. ADNI, initially proposed as a study to investigate biomarkers of AD pathology, has also helped elucidate the impact of asymptomatic cerebrovascular brain injury on cognition within a cohort relatively free of vascular disease. Future ADNI work will emphasize additional vascular biomarkers. Highlights White matter hyperintensities (WMHs) are common to advancing age and likely reflect brain vascular injury among older individuals. WMH and to a lesser extent, magnetic resonance (MR) infarcts, affect risk for transition to cognitive impairment. WMHs and MR infarcts are present, even among Alzheimer's Disease Neuroimaging Initiative (ADNI) participants highly selected to have Alzheimer's disease (AD) as the primary pathology. WMH burden in ADNI is greater among individuals with cognitive impairment and has been associated with AD neurodegenerative markers and cerebral amyloidosis. The negative additive effects of cerebrovascular disease appear present, even in select populations, and future biomarker work needs to further explore this relationship.

Abstract Lead (Pb) poisoning is a significant threat to Aotearoa New Zealand's endangered kea ( Nestor notabilis ), an avian species important to Māori. Historically, exposure was thought to be from lead‐containing building materials; however, recent field observations suggest lead‐based ammunition as an additional source. We used stable lead isotopes to investigate the sources of lead to kea. Comparing 207 Pb/ 206 Pb ratios in kea blood ( n = 91) to both ammunition and building materials, we found approximately one‐third of exposed kea (blood lead > 10 µg/dL) had lead isotope ratios consistent with exposure to lead‐based ammunition. As lead ammunition is still used, including in government‐sponsored culling programs, our data indicate an urgent need to shift toward non‐lead ammunition use to prevent further poisoning and aid conservation efforts. Collaborating with tangata whenua /Māori guardians, we advocate for immediate policy changes to eliminate lead‐based ammunition in kea habitat to safeguard this endangered culturally treasured species from extinction.

AbstractINTRODUCTIONRecent technological advances have increased the risk that de‐identified brain images could be re‐identified from face imagery. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a leading source of publicly available de‐identified brain imaging, who quickly acted to protect participants’ privacy.METHODSAn independent expert committee evaluated 11 face‐deidentification (“de‐facing”) methods and selected four for formal testing.RESULTSEffects of de‐facing on brain measurements were comparable across methods and sufficiently small to recommend de‐facing in ADNI. The committee ultimately recommended mri_reface for advantages in reliability, and for some practical considerations. ADNI leadership approved the committee's recommendation, beginning in ADNI4.DISCUSSIONADNI4 de‐faces all applicable brain images before subsequent pre‐processing, analyses, and public release. Trained analysts inspect de‐faced images to confirm complete face removal and complete non‐modification of brain. This paper details the history of the algorithm selection process and extensive validation, then describes the production workflows for de‐facing in ADNI.Highlights ADNI is implementing “de‐facing” of MRI and PET beginning in ADNI4. “De‐facing” alters face imagery in brain images to help protect privacy. Four algorithms were extensively compared for ADNI and mri_reface was chosen. Validation confirms mri_reface is robust and effective for ADNI sequences. Validation confirms mri_reface negligibly affects ADNI brain measurements.

Abstract The magnetic resonance imaging (MRI) Core has been operating since Alzheimer's Disease Neuroimaging Initiative's (ADNI) inception, providing 20 years of data including reliable, multi‐platform standardized protocols, carefully curated image data, and quantitative measures provided by expert investigators. The overarching purposes of the MRI Core include: (1) optimizing and standardizing MRI acquisition methods, which have been adopted by many multicenter studies and trials worldwide and (2) providing curated images and numeric summary values from relevant MRI sequences/contrasts to the scientific community. Over time, ADNI MRI has become increasingly complex. To remain technically current, the ADNI MRI protocol has changed substantially over the past two decades. The ADNI 4 protocol contains nine different imaging types (e.g., three dimensional [3D] T1‐weighted and fluid‐attenuated inversion recovery [FLAIR]). Our view is that the ADNI MRI data are a greatly underutilized resource. The purpose of this paper is to educate the scientific community on ADNI MRI methods and content to promote greater awareness, accessibility, and use. Highlights The MRI Core provides multi‐platform standardized protocols, carefully curated image data, and quantitative analysis by expert groups. The ADNI MRI protocol has undergone major changes over the past two decades to remain technically current. As of April 25, 2024, the following numbers of image series are available: 17,141 3D T1w; 6877 FLAIR; 3140 T2/PD; 6623 GRE; 3237 dMRI; 2846 ASL; 2968 TF‐fMRI; and 2861 HighResHippo (see Table 1 for abbreviations). As of April 25, 2024, the following numbers of quantitative analyses are available: FreeSurfer 10,997; BSI 6120; tensor based morphometry (TBM) and TBM‐SYN 12,019; WMH 9944; dMRI 1913; ASL 925; TF‐fMRI NFQ 2992; and medial temporal subregion volumes 2726 (see Table 4 for abbreviations). ADNI MRI is an underutilized resource that could be more useful to the research community.

INTRODUCTION: Esophageal adenocarcinoma (EAC) is the second-most lethal cancer in the United States, with Barrett esophagus (BE) being the strongest risk factor. Assessing the future risk of neoplastic progression in patients with BE is difficult; however, high-grade dysplasia (HGD) and early EAC are treatable by endoscopic eradication therapy (EET), with survival rates of 90%. Thus, it would be beneficial to develop a molecular assay to identify high-risk patients, who merit more frequent endoscopic surveillance or EET, as well as low-risk patients, who can avoid EET and undergo less frequent surveillance. METHODS: Deidentified endoscopic biopsies were acquired from 240 patients with BE at 6 centers and confirmed as future progressors or nonprogressors. Tissues were analyzed by a set of methylation-specific biomarker assays. Test performance was assessed in an independent validation set using 4 stratification levels: low risks, low-moderate risks, high-moderate risks, and high risks. RESULTS: Relative to patients in the low-risk group, high-risk patients were 15.2 times more likely to progress within 5 years to HGD or EAC. For patients in the high-risk category, the average risk of progressing to HGD or EAC within 5 years was 21.5%, 4-fold the BE population prevalence within 5 years, whereas low-risk patients had a progression risk of only 1.85%. DISCUSSION: This clinical assay, Esopredict, stratifies future neoplastic progression risk to identify higher-risk patients with BE who can benefit from EET or more frequent surveillance and lower-risk patients who can benefit from reduced surveillance.