18F-3'-Deoxy-3'-Fluorothymidine Positron Emission Tomography Imaging for the Prediction of Acute Graft-Versus-Host Disease in Mouse Hematopoietic Stem Cell Transplant Models.

Acute graft-versus-host disease (aGVHD) remains a barrier to the success of allogeneic hematopoietic stem cell transplantation. In mice, studies have demonstrated that donor conventional T cells traffic into host secondary lymphoid tissues early after transplant, and that this process is critical for the development of disease. As a result, the measurement of cellular proliferation within lymphoid sites early after transplant might be a useful approach for predicting aGVHD in humans. 18F-3'-deoxy-3'-fluorothymidine (FLT) positron emission tomography (PET) imaging has recently emerged as a functional imaging modality in oncology patients. FLT, a thymidine analog, is incorporated into replicating DNA and is thus an indirect marker of cellular proliferation. Here we report that FLT PET imaging can differentiate mice receiving alloreactive T cells and destined to develop lethal aGVHD from control mice. Mice receiving allogeneic T cells demonstrated a stronger FLT signal within the peripheral lymph nodes compared with control mice at all time points after transplant. In addition, allogeneic T cell recipients transiently demonstrated stronger FLT uptake within the spleen. Importantly, these differences were apparent before the development of clinical disease. In contrast, the FLT signal within the host bowel, an important aGVHD target organ, was more variable after transplant and was not consistently different between aGVHD mice and control mice. Collectively, these findings suggest that the imaging of patient lymphoid sites using existing FLT PET technology might be useful for predicting aGVHD in the clinical setting.

The 43rd International Society for Computerized Electrocardiology ECG initiative for the automated detection of strict left bundle branch block.

The presence of left bundle branch block (LBBB) is an important predictor of benefit from cardiac resynchronization therapy (CRT). New "strict" electrocardiographic (ECG) criteria for LBBB have been shown to better predict benefit from CRT. The "strict" LBBB criteria include: QRS duration ≥140 ms (men) or ≥130 ms (women), QS- or rS-configurations of the QRS complex in leads V1 and V2, and mid-QRS notching or slurring in ≥2 of leads V1, V2, V5, V6, I and aVL. The "strict" LBBB criteria are not regularly used and most hospital automated ECG systems and physicians still use more conventional LBBB criteria. As part of the 43rd International Society for Computerized Electrocardiology (ISCE) meeting, we conducted an initiative on the automated detection of "strict" LBBB where industry and academic investigators could present their algorithm results on digital 12-lead ECGs with varying QRS morphologies from the MADIT-CRT trial (300 training and 302 test set ECGs that were manually adjudicated for "strict" LBBB presence). The results revealed a 64-82% accuracy, 48-76% sensitivity and 46-87% specificity for automated "strict" LBBB detection from 7 participants. Most mismatches were likely attributed to differences in detection and absence of specific definitions for notches and slurs while differences in QRS duration and S-waves in leads V1 and V2 were less problematic. The full unblinded training and test datasets including all ECG signals are being made available through the Telemetric and Holter ECG Warehouse (THEW) for further exploration.

Dynamic perfluorinated gas MRI reveals abnormal ventilation despite normal FEV1 in cystic fibrosis.

We hypothesized that dynamic perfluorinated gas MRI would sensitively detect mild cystic fibrosis (CF) lung disease. This cross-sectional study enrolled 20 healthy volunteers and 24 stable subjects with CF, including a subgroup of subjects with normal forced expiratory volume in the first second (FEV1; >80% predicted, n = 9). Dynamic fluorine-19-enhanced MRI (19F MRI) were acquired during sequential breath holds while breathing perfluoropropane (PFP) and during gas wash-out. Outcomes included the fraction of lung without significant ventilation (ventilation defect percent, VDP) and time constants that described PFP wash-in and wash-out kinetics. VDP values (mean ± SD) of healthy controls (3.87% ± 2.7%) were statistically different from moderate CF subjects (19.5% ± 15.5%, P = 0.001) but not from mild CF subjects (10.4% ± 9.9%, P = 0.24). In contrast, the fractional lung volume with slow gas wash-out was elevated both in subjects with mild (9.61% ± 4.87%; P = 0.0066) and moderate CF (16.01% ± 5.01%; P = 0.0002) when compared with healthy controls (3.84% ± 2.16%) and distinguished mild from moderate CF (P = 0.006). 19F MRI detected significant ventilation abnormalities in subjects with CF. The ability of gas wash-out kinetics to distinguish between healthy and mild CF lung disease subjects makes 19F MRI a potentially valuable method for the characterization of early lung disease in CF. This study has been registered at ClinicalTrials.gov (NCT03489590).