Optimizing the efficiency of high-field multivoxel spectroscopic imaging by multiplexing in space and time.

A new strategy to yield information from the maximum number of voxels, each at the optimum signal-to-noise ratio (SNR) per unit time, in MR spectroscopic imaging (MRSI) is introduced. In the past, maximum acquisition duty-cycle was obtained by multiplexing in time several single slices each repetition time (TR), while optimal SNR was achieved by encoding the entire volume of interest (VOI) each TR. We show that optimal SNR and acquisition efficiency can both be achieved simultaneously by multiplexing in space and time several slabs of several slices, each. Since coverage of common VOIs in 3D proton MRSI in the human brain typically requires eight or more slices, at 3 T or higher magnetic fields, two or more slabs can fit into the optimum TR (approximately 1.6 s). Since typically four or less slices would then fit into each slab, Hadamard encoding is favored in that direction for slice profile reasons. It is demonstrated that per fixed examination length, the new method gives, at 3 T, twice as many voxels, each of the same SNR and size, compared with current 3D chemical shift imaging techniques. It is shown that this gain will increase for more extensive spatial coverage or higher fields.     

口服二巯基丁二酸治疗狗路易氏剂中毒

为证实口服二巯基丁二酸（ＤＭＳＡ）治疗路易氏剂中毒的效价，以狗为实验动物，进行实验治疗研究，狗口服ＤＭＳＡ（４０～１２０ｍｇ／ｋｇ）后，２周内未见到有关的生理，生化指标明显变化，该药毒性较小。ＤＭＳＡ可在肠道内较好地被吸收，与静脉注射途径比较，口服组血药浓度上升慢，下降亦慢，可在体内维持较长时间，ＤＭＳＡ在体内促排砷的作用与静脉注射同剂量ＤＭＳＡ（钠盐）相当。狗口服ＤＭＳＡ４０ｍｇ／ｋｇ可对抗路易     

Patterns of healing of scaphoid fractures. The importance of vascularity

We studied 45 patients with 46 fractures of the scaphoid who presented sequentially over a period of 21 months. MRI enabled us to relate the pattern of the fracture to the blood supply of the scaphoid. Serial MRI studies of the four main patterns showed that each followed a constant sequence during healing and failure to progress normally predicted nonunion.     

Hemorrhage associated with “bone crisis” in Gaucher's disease identified by magnetic resonance imaging

Children suffering from Gaucher's disease were examined by magnetic resonance imaging (MRI) during a characteristic episode of bone crisis. An unexpectedly high intramedullary as well as subperiosteal signal was observed on both the T1 and T2-weighted sequences in 5 patients, suggesting a subacute hemorrhage or hematoma. It is conceivable that such a painful hemorrhage is an important component of the bone crisis phenomenon. Furthermore, in these cases this is a specific sign which may enable differentiation of bone crises from other types of bone pain associated with Gaucher's disease.     

Postoperative management of Dupuytren’s disease with topical nitroglycerin

Dupuytren’s contracture remains a significant clinical challenge due to associated complications and a recurrence rate of up to 60%. Commonly, the operated skin tends to rebuild scar in the area of surgery. Assuming local ischemia as an etiological factor, two cases in which topical nitroglycerin was used following surgical treatment of Dupuytren’s disease are presented. In these patients, no raised scar formation developed during healing. At least six months after surgery, disease recurrence was not noted and the patients and surgeon reported improved skin quality. In the present study, the use of topical nitroglycerin, a local vasodilator, appeared to prevent recurrent scar formation, possibly through prevention of local ischemia. Further study and follow-up is necessary.     

Functional magnetic resonance imaging monitoring of pathological changes in rodent livers during hyperoxia and hypercapnia

Liver diseases and regeneration are associated with hemodynamic changes denoting pathological alterations. Determining and monitoring physiological and pathological liver changes is essential for diagnostic and therapeutic objectives. Our aim was to determine the feasibility of functional magnetic resonance imaging (fMRI) during hypercapnia and hyperoxia for monitoring liver pathology. Liver fMRI images were acquired in rodents following acute bleeding, partial hepatectomy, and fibrosis. Results were quantitated and confirmed by histology. Changes induced by hyperoxia and hypercapnia following hemorrhage significantly correlated with the percentage of blood loss, reflecting lower liver perfusion and diminished vessel responsiveness to gas saturation. Hepatectomy resulted in an early decline in signal intensity changes due to hyperoxia, suggesting a decrease in liver perfusion and blood content. Following hepatectomy, signal intensity changes due to hypercapnia increased, signifying a change in liver perfusion from a mainly portal to a more arterial source. Two weeks after induction of fibrosis, signal intensity changes due to hypercapnia became much lower and those due to hyperoxia were much higher than those in normal livers, reflecting the increased perfusion due to the inflammatory process as confirmed by histologic analysis. With fibrosis progression, signal intensity changes induced by hypercapnia and hyperoxia were gradually attenuated, indicating structural and functional alterations of the liver vasculature during fibrosis. CONCLUSION: In various liver pathologies, fMRI response to hypercapnia and hyperoxia is sensitive to changes in liver hemodynamic status involved in hepatic damage or recovery; thus, this technique may offer an additional noninvasive diagnostic tool for evaluation and follow-up of liver diseases by means of examining perfusion-related alterations.     

Antibody Drug Conjugates: Preclinical Considerations

The development path for antibody drug conjugates (ADCs) is more complex and challenging than for unmodified antibodies. While many of the preclinical considerations for both unmodified and antibody drug conjugates are shared, special considerations must be taken into account when developing an ADC. Unlike unmodified antibodies, an ADC must preferentially bind to tumor cells, internalize, and traffic to the appropriate intracellular compartment to release the payload. Parameters that can impact the pharmacological properties of this class of therapeutics include the selection of the payload, the type of linker, and the methodology for payload drug conjugation. Despite a plethora of in vitro assays and in vivo models to screen and evaluate ADCs, the challenge remains to develop improved preclinical tools that will be more predictive of clinical outcome. This review will focus on preclinical considerations for clinically validated small molecule ADCs. In addition, the lessons learned from Mylotarg®, the first in class FDA-approved ADC, are highlighted.     

Cytocompatibility of novel extracellular matrix protein analogs of biodegradable polyester polymers derived from α-hydroxy amino acids

One of the challenges in regenerative medicine is the development of novel biodegradable materials to build scaffolds that will support multiple cell types for tissue engineering. Here we describe the preparation, characterization, and cytocompatibility of homo- and hetero-polyesters of α-hydroxy amino acid derivatives with or without lactic acid conjugation. The polymers were prepared by a direct condensation method and characterized using gel permeation chromatography, ¹H-nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, optical activity, and solubility. The surface charge of the polymers was evaluated using zeta potential measurements. The polymers were coated onto glass cover slips followed by characterization using nano-surface profiler, thin film reflectometry, and atomic force microscopy (AFM). Their interaction with endothelial and neuronal cells was assessed using adhesion, proliferation, and differentiation assays. Of the characterized polymers, Poly-HOVal-LA, but not Poly-(D)HOPhe, significantly augmented nerve growth factor (NGF)-induced neuronal differentiation of the PC12 pheochromcytoma cells. In contrast, Poly-HOLeu increased by 20% the adhesion of endothelial cells, but did not affect PC12 cell differentiation. NGF-induced Erk1/2 phosphorylation in PC12 cells grown on the different polymers was similar to the effect observed for cells cultured on collagen type I. While no significant association could be established between charge and the differentiative/proliferative properties of the polymers, AFM analysis indicated augmentation of NGF-induced neuronal differentiation on smooth polymer surfaces. We conclude that overall selective cytocompatibility and bioactivity might render α-hydroxy amino acid polymers useful as extracellular matrix-mimicking materials for tissue engineering.     

The association between systolic blood pressure reduction during clonidine suppression testing and the decrease in plasma catecholamines and metanephrines

Borderline isolated norepinephrine (NE) and normetanephrine (NMT) elevation is common among patients with suspected pheochromocytoma and paraganglioma (PPGL). The clonidine suppression test (CST) may help establish the etiology in these cases. Prolonged laboratory processing and/or paucity of reliable biochemical assays may limit the utility of CST. The aim of this study was to evaluate whether blood pressure (BP) reduction during CST is associated with alterations in plasma NMT/NE, thereby potentially providing an immediate indication of CST results. In this cross‐sectional study, the authors included all consecutive patients with suspected PPGL who underwent CST from January 1, 2014, to December 31, 2019. Linear regression models were conducted to evaluate the association between BP reduction and decrease in plasma NMT/NE. The final analysis included 36 patients (17 males). The decrease in systolic BP (SBP) 90 minutes postclonidine was associated with a decrease in plasma NMT (R = 0.668, P = .025) and NE (R = 0.562, P = .005). A 40% decrease in NMT and NE correlated with a 9.74% and 7.16% decrease in SBP, respectively. Subgroup analyses demonstrated that the association between SBP reduction and the decrease in plasma NMT (R = 0.764, P = .046) and NE (R = 0.714, P = .003) strengthens among patients with hypertension and among those with diabetes mellitus (R = 0.974, P = .026 for NMT). In conclusion, SBP reduction during CST is associated with plasma NMT and NE decrease. Therefore, the decrease in SBP 90 minutes postclonidine may serve as an immediate complementary clinical tool for PPGL diagnosis.