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Quantitative imaging biomarkers (QIBs) can be defined as objective measures that are sensitive and specific to changes in tissue physiology. Provided the acquired QIBs are not affected by scanner changes, they could play an important role in disease diagnosis, prognosis, management, and treatment monitoring. The precision of selected QIBs was assessed from data collected on a 3-T scanner in four healthy participants over a 5-year period. Inevitable scanner changes and acquisition protocol revisions occurred during this time. Standard and custom processing pipelines were used to calculate regional brain volume, cortical thickness, T2, T2*, quantitative susceptibility, cerebral blood flow, axial, radial and mean diffusivity, peak width of skeletonized mean diffusivity, and fractional anisotropy from the acquired images. Coefficient of variation (CoV) and intra-class correlation (ICC) indices were determined in the short-term (i.e., repeatable over three acquisitions within 4 weeks) and in the long-term (i.e., reproducible over four acquisition sessions in 5 years). Precision indices varied based on acquisition technique, processing pipeline, and anatomical region. Good repeatability (average CoV=2.40% and ICC=0.78) and reproducibility (average CoV=8.86 % and ICC=0.72) were found over all QIBs. The best performance indices were obtained for diffusion derived biomarkers (CoV∼0.96% and ICCs=0.87); conversely, the poorest indices were found for the cerebral blood flow biomarker (CoV>10% and ICC<0.5). These results demonstrate that changes in protocol, along with hardware and software upgrades, did not affect the estimates of the selected biomarkers and their precision. Further characterization of the QIB is necessary to understand meaningful changes in the biomarkers in longitudinal studies of normal brain aging and translation to clinical research., Competing Interests: Conflict of Interest The authors have no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Background and Purpose: We investigated the sensitivity and reliability of MRI susceptibility-weighted imaging (SWI) compared with routine MRI T2*-weighted gradient-recalled echo (GRE) for cerebral microbleed (CMB) detection., Methods: We used data from a prospective study of cerebral amyloid angiopathy (n=9; mean age, 71±8.3) and healthy non-cerebral amyloid angiopathy controls (n=22; mean age, 68±6.3). Three raters (labeled 1, 2, and 3) independently interpreted the GRE and SWI sequences (using the phase-filtered magnitude image) blinded to clinical information., Results: In 9 cerebral amyloid angiopathy cases, the raters identified 1146 total CMBs on GRE and 1432 CMBs on SWI. In 22 healthy control subjects, the raters identified ≥1 CMBs in 6/22 on GRE (total 9 CMBs) and 5/22 on SWI (total 19 CMBs). Among cerebral amyloid angiopathy cases, the reliability between raters for CMB counts was good for SWI (intraclass correlation coefficient, 0.87) but only moderate for GRE (intraclass correlation coefficient, 0.52). In controls, agreement on the presence or absence of CMBs in controls was moderate to good on both SWI (κ coefficient ranged from 0.57 to 0.74 across the 3 combinations of rater pairs) and GRE (κ range, 0.31 to 0.70). A review of 114 hypointensities identified as possible CMBs indicated that increased detection and reliability on SWI was related to both increased contrast and higher resolution, allowing better discrimination of CMBs from the background and better anatomic differentiation from pial vessels., Conclusions: SWI confers greater reliability as well as greater sensitivity for CMB detection compared with GRE, and should be the preferred sequence for quantifying CMB counts.

Background and Purpose: Definitions for chronic lacunar infarcts vary. Recent retrospective studies suggest that many acute lacunar strokes do not develop a cavitated appearance. We determined the characteristics of acute lacunar infarcts on follow-up MRI in consecutive patients participating in prospective research studies., Methods: Patients with acute lacunar infarction on diffusion-weighted imaging were selected from 3 prospective cohort studies of minor stroke imaged within <24 hours of onset. Follow-up MRI was performed at 30 days (Vascular Imaging of Acute Stroke for Identifying Predictors of Clinical Outcome and Recurrent Ischemic Events [VISION] study, n=21) or 90 days (VISION-2 and CT and MRI in the Triage of TIA and Minor Cerebrovascular Events to Identify High Risk Patients [CATCH] studies, n=34). Evidence of cavitation on MRI was rated separately on fluid-attenuated inversion recovery, T1, and T2 sequences by 2 independent study physicians; discrepant readings were resolved by consensus., Results: Probable or definite cavitation on any sequence was more common at 90 days compared with 30 days (P≤0.001 for all sequences). At 90 days, evidence of cavitation was seen on at least 1 sequence in 33 of 34 patients (97%). The T1-weighted sequence was most sensitive to the presence of cavitation (94% at 90 days). By contrast, the fluid-attenuated inversion recovery sequence frequently failed to show evidence of cavitation in the brain stem or thalamus (only 10 of 18 [56%] showed cavitation)., Conclusions: MRI scanning at 90 days with T1-weighted imaging reveals evidence of cavitation in nearly all cases of acute lacunar infarction. By contrast, reliance on fluid-attenuated inversion recovery alone will miss many cavitated lesions in the thalamus and brain stem. These factors should be taken into account in the development of standardized criteria for lacunar infarction on MRI.

We describe MR imaging findings applying gradient echo (GRE) T2*-weighted and fluid-attenuated inversion recovery (FLAIR) MR images at 3T to three patients with hyperacute subarachnoid and intraventricular hemorrhage from ruptured aneurysms. Hyperacute subarachnoid and intraventricular hemorrhages (SAH and IVH) were more clearly visualized as an area of decreased signal intensity on GRE T2*-weighted sequences than on FLAIR sequences in all three patients. These preliminary results suggest that acute SAH and IVH with GRE T2*-weighted imaging can be reliably diagnosed at 3T.

Poxviruses are large DNA viruses that replicate in the cytoplasm of infected cells and recombine at high frequencies. Calcium phosphate precipitates were used to cotransfect Shope fibroma virus-infected cells with different DNA substrates and the recombinant products assayed by genetic and biochemical methods. We have shown previously that bacteriophage lambda DNAs can be used as substrates in these experiments and recombinants assayed on Escherichia coli following DNA recovery and in vitro packaging. Using this assay it was observed that 2-3% of the phage recovered from crosses between point mutants retained heteroduplex at at least one of the mutant sites. The reliability of this genetic analysis was confirmed using DNA substrates that permitted the direct detection of heteroduplex molecules by denaturant gel electrophoresis and Southern blotting. It was further noted that heteroduplex formation coincided with the onset of both replication and recombination suggesting that poxviruses, like certain bacteriophage, make no clear biochemical distinction between these three processes. The fraction of heteroduplex molecules peaked about 12-hr postinfection then declined later in the infection. This decline was probably due to DNA replication rather than mismatch repair because, while high levels of induced DNA polymerase persisted beyond the time of maximal heteroduplex recovery, we were unable to detect any type of mismatch repair activity in cytoplasmic extracts. These results suggest that, although heteroduplex molecules are formed during the progress of poxviral infection, gene conversion through mismatch repair probably does not produce most of the recombinants. The significance of these observations are discussed considering some of the unique properties of poxviral biology.