White matter microstructure associations to amyloid burden in adults with Down syndrome.

INTRODUCTION: Individuals with Down syndrome (DS) are at an increased risk of developing Alzheimer's Disease (AD). One of the early underlying mechanisms in AD pathology is the accumulation of amyloid protein plaques, which are deposited in extracellular gray matter and signify the first stage in the cascade of neurodegenerative events. AD-related neurodegeneration is also evidenced as microstructural changes in white matter. In this work, we explored the correlation of white matter microstructure with amyloid load to assess amyloid-related neurodegeneration in a cohort of adults with DS. METHODS: In this study of 96 adults with DS, the relation of white matter microstructure using diffusion tensor imaging (DTI) and amyloid plaque burden using [11C]PiB PET were examined. The amyloid load (AβL) derived from [11C]PiB was used as a global measure of amyloid burden. AβL and DTI measures were compared using tract-based spatial statistics (TBSS) and corrected for imaging site and chronological age. RESULTS: TBSS of the DTI maps showed widespread age-by-amyloid interaction with both fractional anisotropy (FA) and mean diffusivity (MD). Further, diffuse negative association of FA and positive association of MD with amyloid were observed. DISCUSSION: These findings are consistent with the white matter microstructural changes associated with AD disease progression in late onset AD in non-DS populations

The impact of arterial input function determination variations on prostate dynamic contrast-enhanced magnetic resonance imaging pharmacokinetic modeling: a multicenter data analysis challenge, part II

This multicenter study evaluated the effect of variations in arterial input function (AIF) determination on pharmacokinetic (PK) analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data using the shutter-speed model (SSM). Data acquired from eleven prostate cancer patients were shared among nine centers. Each center used a site-specific method to measure the individual AIF from each data set and submitted the results to the managing center. These AIFs, their reference tissue-adjusted variants, and a literature population-averaged AIF, were used by the managing center to perform SSM PK analysis to estimate Ktrans (volume transfer rate constant), ve (extravascular, extracellular volume fraction), kep (efflux rate constant), and τi (mean intracellular water lifetime). All other variables, including the definition of the tumor region of interest and precontrast T1 values, were kept the same to evaluate parameter variations caused by variations in only the AIF. Considerable PK parameter variations were observed with within-subject coefficient of variation (wCV) values of 0.58, 0.27, 0.42, and 0.24 for Ktrans, ve, kep, and τi, respectively, using the unadjusted AIFs. Use of the reference tissue-adjusted AIFs reduced variations in Ktrans and ve (wCV = 0.50 and 0.10, respectively), but had smaller effects on kep and τi (wCV = 0.39 and 0.22, respectively). kep is less sensitive to AIF variation than Ktrans, suggesting it may be a more robust imaging biomarker of prostate microvasculature. With low sensitivity to AIF uncertainty, the SSM-unique τi parameter may have advantages over the conventional PK parameters in a longitudinal study

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

The reality of the incarnation

https://place.asburyseminary.edu/ecommonsatschapelservices/6997/thumbnail.jp

The Life And Teachings Of Jesus

New York336 p.; 23 c

Calcified Lymph Nodes Causing Clinically Relevant Attenuation Correction Artifacts on PET/CT Imaging

There are several artifacts unique to PET/CT imaging, with CT-based attenuation correction (AC) artifacts being among the most commonly reported. AC artifacts from calcified lymph nodes represent clinically significant and easily misinterpreted PET/CT artifacts that have received little attention in the literature. In this case series, we report three cases of calcified lymph nodes causing an AC artifact and one case of a highly calcified lymph node without an AC artifact. All three cases of calcified lymph nodes causing an AC artifact would have resulted in a change in patient staging, and likely management, if the nodes had been misinterpreted as malignant nodes. In PET/CT imaging, this artifact needs to be considered as a potential cause of apparent FDG activity when calcified lymph nodes are present on the CT portion of a PET/CT study in order to avoid misinterpretation and potential patient mismanagement

Assessment of Early Therapy Response with F-18-FLT PET in Glioblastoma Multiforme

Early therapy response assessment in glioblastoma multiforme remains a challenge. Evaluation by MRI relies on changes in tumor contrast enhancement or size, which are usually not visible at early therapy response assessment times. In addition, MRI may not be reliable for early therapy response assessment if only molecular changes have occurred. PET with F-18-FLT, a tracer associated with cellular proliferation, has been proposed as a potential method of early therapy response assessment and is an area of active research. We present a case where early response assessment with F-18-FLT PET was associated with a favorable 1-year follow-up outcome

[18F]ML-10 PET: Initial Experience in Glioblastoma Multiforme Therapy Response Assessment

The ability to assess tumor apoptotic response to therapy could provide a direct and prompt measure of therapeutic efficacy. 18F-labeled 2-(5-fluoro-pentyl)-2-methyl-malonic acid ([18F]ML-10) is proposed as a positron emission tomography (PET) apoptosis imaging radiotracer. This manuscript presents initial experience using [18F]ML-10 PET to predict therapeutic response in 4 patients with human glioblastoma multiforme. Each patient underwent [18F]ML-10 PET and contrast-enhanced magnetic resonance imaging (MRI) before (baseline) and at ∼2–3 weeks after therapy (early-therapy assessment). All PET and MRI data were acquired using a Siemens BioGraph mMR integrated PET/MRI scanner. PET acquisitions commenced 120 minutes after injection with 10 mCi of [18F]ML-10. Changes in [18F]ML-10 standard uptake values were assessed in conjunction with MRI changes. Time-to-progression was used as the outcome measure. One patient, ML-10 #4, underwent additional sodium-23 (23Na) MRI at baseline and early-therapy assessment. Siemens 3 T Magnetom Tim Trio scanner with a dual-tuned (1H-23Na) head coil was used for 23Na-MRI, acquiring two three-dimensional single-quantum sodium images at two echo times (TE). Volume-fraction-weighted bound sodium concentration was quantified through pixel-by-pixel subtraction of the two single-quantum sodium images. In the cases presented, [18F]ML-10 uptake changes were not clearly related to time-to-progression. We suggest that this may be because the tumors are undergoing varying rates of cell death and growth. Acquisition of complementary measures of tumor cell proliferation or viability may aid in the interpretation of PET apoptosis imaging