The potential of dynamic 99mTc-sestamibi cadmium zinc telluride-single-photon emission computed tomography camera assessing myocardial flow reserve in patients with heart failure with preserved ejection fraction.

Aims: Coronary microvascular dysfunction (CMD) is related to the pathophysiology, mortality, and morbidity of heart failure with preserved ejection fraction (HFpEF). A novel single-photon emission computed tomography (SPECT) camera with cadmium zinc telluride (CZT) detectors allows for the quantification of absolute myocardial blood flow and myocardial flow reserve (MFR) in patients with coronary artery disease. However, the potential of CZT-SPECT assessing for CMD has never been evaluated in patients with HFpEF. Methods and results: The clinical records of 127 consecutive patients who underwent dynamic CZT-SPECT were retrospectively reviewed. Rest and stress scanning were started simultaneously with 3 and 9 MBq/kg of 99mTc-sestamibi administration, respectively. Dynamic CZT-SPECT imaging data were analysed using a net-retention model with commercially available software. Transthoracic echocardiography was performed in all patients. The MFR value was significantly lower in the HFpEF group (mean ± SEM = 2.00 ± 0.097) than that in the non-HFpEF group (mean ± SEM = 2.74 ± 0.14, P = 0.0004). A receiver operating characteristic analysis indicated that if a cut-off value of 2.525 was applied, MFR could efficiently distinguish HFpEF from non-HFpEF. Heart failure with preserved ejection fraction had a consistently low MFR, regardless of the diastolic dysfunction score. Heart failure with preserved ejection fraction patients with MFR values lower than 2.075 had a significantly higher incidence of heart failure exacerbation. Conclusion: Myocardial flow reserve assessed by CZT-SPECT was significantly reduced in patients with HFpEF. A lower MFR was associated with a higher hospitalization rate in these patients. Myocardial flow reserve assessed by CZT-SPECT has the potential to predict future adverse events and stratify the severity of disease in patients with HFpEF.

FLASHlight MRI in real time-a step towards Star Trek medicine.

This work describes a dynamic magnetic resonance imaging (MRI) technique for local scanning of the human body with use of a handheld receive coil or coil array. Real-time MRI is based on highly undersampled radial gradient-echo sequences with joint reconstructions of serial images and coil sensitivity maps by regularized nonlinear inversion (NLINV). For this proof-of-concept study, a fixed slice position and field-of-view (FOV) were predefined from the operating console, while a local receive coil (array) is moved across the body-for the sake of simplicity by the subject itself. Experimental realizations with a conventional 3 T magnet comprise dynamic anatomic imaging of the head, thorax and abdomen of healthy volunteers. Typically, the image resolution was 0.75 to 1.5 mm with 3 to 6 mm section thickness and acquisition times of 33 to 100 ms per frame. However, spatiotemporal resolutions and contrasts are highly variable and may be adjusted to clinical needs. In summary, the proposed FLASHlight MRI method provides a robust acquisition and reconstruction basis for future diagnostic strategies that mimic the usage of ultrasound. Necessary extensions for this vision require remote control of all sequence parameters by a person at the scanner as well as the design of more flexible gradients and magnets.

Biophysical Methods for Characterization of Antibody-Drug Conjugates.

Antibody-drug conjugates (ADC) are made up of three components: (1) a mAb specific to cells of choice, (2) a small molecule with desired end goal, and (3) a linker to covalently link drug molecule to the antibody. Bringing together the mAb, drug molecule, and the linker results in the formation of an immunoconjugate designed to selectively deliver the drug molecule to a cell of interest. Synergic effects of the mAb and drug molecule lead to destroying the target tumor cells while leaving the normal cells unharmed. However, the development of ADCs is associated with challenges due to the heterogeneity of the ADC molecules created from the conjugation process. Addition of the linker and drug moieties during processing as well as the hydrophobicity of the drug itself can lead to structural changes that may affect the stability and functional profile of the conjugated molecule. Furthermore, linkers site of attachment plays a major role in determining the conformational and colloidal properties of the ADCs. In this chapter, several characterization methods are introduced to determine the biophysical characteristics of the ADC. Protocols, data analysis as well as notes for circular dichroism, intrinsic fluorescence, ANS fluorescence, differential scanning calorimetry, and dynamic scanning fluorimetry are outlined in detail.

Forward to the Past: The Case for Quantitative PET Imaging.

PET was developed in the 1970s as an in vivo method to measure regional pathophysiologic processes. In the 1990s the focus moved to the detection of local increases in uptake, first in the brain (activation studies) and later in oncology (finding metastases), with 18F-FDG emerging as a highly sensitive staging technique. This focus on sensitivity has overshadowed the other main characteristic of PET, its quantitative nature. In recent years there has been a shift. PET is now seen as a promising tool for drug development and precision medicine-that is, a method to monitor or even predict response to therapy. Quantification is essential for precision medicine, but many studies today use simplified semiquantitative methods without properly validating them. This review provides several examples illustrating that simplified methods may lead to less accurate or even misleading results. Simplification is important for routine clinical practice, but finding the optimal balance between accuracy and simplicity requires careful studies. It is argued that the use of simplified approaches without proper validation not only may waste time and resources but also may raise ethical questions, especially in drug development studies.