Traumatic brain injury imaging research roadmap.

The past decade has seen impressive advances in the types of neuroimaging information that can be acquired in patients with traumatic brain injury. However, despite this increase in information, understanding of the contribution of this information to prognostic accuracy and treatment pathways for patients is limited. Available techniques often allow us to infer the presence of microscopic changes indicative of alterations in physiology and function in brain tissue. However, because histologic confirmation is typically lacking, conclusions reached by using these techniques remain solely inferential in almost all cases. Hence, a need exists for validation of these techniques by using data from large population samples that are obtained in a uniform manner, analyzed according to well-accepted procedures, and correlated with closely monitored clinical outcomes. At present, many of these approaches remain confined to population-based research rather than diagnosis at an individual level, particularly with regard to traumatic brain injury that is mild or moderate in degree. A need and a priority exist for patient-centered tools that will allow advanced neuroimaging tools to be brought into clinical settings. One barrier to developing these tools is a lack of an age-, sex-, and comorbidities-stratified, sequence-specific, reference imaging data base that could provide a clear understanding of normal variations across populations. Such a data base would provide researchers and clinicians with the information necessary to develop computational tools for the patient-based interpretation of advanced neuroimaging studies in the clinical setting. The recent "Joint ASNR-ACR HII-ASFNR TBI Workshop: Bringing Advanced Neuroimaging for Traumatic Brain Injury into the Clinic" on May 23, 2014, in Montreal, Quebec, Canada, brought together neuroradiologists, neurologists, psychiatrists, neuropsychologists, neuroimaging scientists, members of the National Institute of Neurologic Disorders and Stroke, industry representatives, and other traumatic brain injury stakeholders to attempt to reach consensus on issues related to and develop consensus recommendations in terms of creating both a well-characterized normative data base of comprehensive imaging and ancillary data to serve as a reference for tools that will allow interpretation of advanced neuroimaging tests at an individual level of a patient with traumatic brain injury. The workshop involved discussions concerning the following: 1) designation of the policies and infrastructure needed for a normative data base, 2) principles for characterizing normal control subjects, and 3) standardizing research neuroimaging protocols for traumatic brain injury. The present article summarizes these recommendations and examines practical steps to achieve them.

Three-dimensional isotropic contrast-enhanced MR angiography of the carotid artery using sensitivity-encoding and random elliptic centric k-space filling: technique optimization.

We present a study that helped optimize a three-dimensional isotropic contrast-enhanced MR angiographic (CE-MRA) technique, using sensitivity encoding (SENSE) and random elliptic centric k-space filling. Two-dimensional gradient-echo sequence (TR/TE/flip angle 3.4/0.97/40 degrees ) was used to generate time-intensity curves in porcine carotid arteries for a fixed dose of Gd-DTPA (0.02 mmol/kg) at the following intravenous injection rates: 0.1, 0.3, 0.5, 1.0, 1.5, 2.0, and 3.0 ml/s. The time of contrast arrival and time to peak were recorded. Based on the time-intensity curves, three-dimensional high-resolution isotropic (1 mm3) CE-MRA sequence (TR/TE/flip angle: 4.9/2.4/30 degrees ), using SENSE (reduction factor of 2) and random elliptic centric k-space filling, was initiated twice for each of the above injection rates: first at the time of contrast arrival and second at the time of peak contrast. The three-dimensional CE-MRA images were analyzed for artifacts, signal-to-noise ratio, and venous contamination. For the three-dimensional CE-MRA acquisitions that were initiated at the time of contrast arrival, there was a gradual improvement in signal-to-noise ratio (SNR) in the carotid arteries with increasing injection rate. The same trend was not observed for the acquisitions that were initiated at the time of peak contrast. SENSE combined with random elliptic k-space acquisition in CE-MRA allows for higher SNR with fewer ringing artifacts at faster contrast injection rates.

Calf muscle cross-sectional area and peak oxygen uptake and work rate in children and adults.

It is often assumed that the inherent peak muscle metabolic capacity scales in direct proportion to muscle cross-sectional area and is the same in small and large animals (A. V. Hill. Sci. Prog. 38: 208-230, 1950). We wondered whether this relationship between size and function was true during the period of growth and development in humans. Magnetic resonance imaging (MRI) was used to determine calf muscle cross-sectional area (CSA) in 20 children (6-11 yr old, 11 boys) and in 18 adults (23-42 yr old, 10 men). Progressive cycle ergometer exercise was performed to determine peak oxygen uptake (VO2peak) and work rate (WRpeak). The scaling factor (determined by allometric analysis) relating maximal O2 uptake (VO2max) to muscle CSA for the whole sample population was 1.04 +/- 0.12 (SE), but the scaling factor relating WRpeak to muscle CSA was significantly greater (1.37 +/- 0.12). Consistent with this, VO2max/CSA was not affected by body weight, but the WRpeak/CSA increased as a function of weight both in males (P < 0.005) and females (P < 0.05). No differences in VO2max/CSA were found between children and adults. WRpeak/CSA was significantly higher in adults compared with children (P < 0.05). It appears that the inherent peak muscle metabolic capacity is smaller in children than in adults. Moreover, the coupling of muscle capacity with whole body metabolic rate changes during growth in humans.

Temperature-induced fusion of small unilamellar vesicles formed from saturated long-chain lecithins and diheptanoylphosphatidylcholine.

Small unilamellar vesicles which form when gel-state long-chain phosphatidylcholines are mixed with micellar short-chain lecithins undergo an increase in size as the long-chain species melts to its liquid-crystalline form. Analysis of the vesicle population with quasi-elastic light scattering shows that the particle size increases from 90-A radius to greater than 5000-A radius. Resonance energy transfer experiments show total mixing of lipid probes with unlabeled vesicles only when the Tm of the long-chain phosphatidylcholine is exceeded. This implies that the large size change represents a fusion process. Aqueous compartments are also mixed during this transition. 31P NMR analysis of the vesicle mixtures above the phase transition shows a great degree of heterogeneity with large unilamellar particles coexisting with oligo- and multilamellar structures. Upon cooling the vesicles below the Tm, the original size distribution (e.g., small unilamellar vesicles) is obtained, as monitored by both quasi-elastic light scattering and 31P NMR spectroscopy. This temperature-induced fusion of unilamellar vesicles is concentration dependent and can be abolished at lower total phospholipid concentrations. It occurs over a wide range of long-chain to short-chain ratios and occurs with 1-palmitoyl-2-stearoylphosphatidylcholine and dimyristoylphosphatidylcholine as well. Characterization of this fusion event is used to understand the anomalous kinetics of water-soluble phospholipases toward these unusual vesicles.

The stereoselectivity of the Clostridium perfringens phospholipase C: hydrolysis of thiophosphate analogs of phosphatidylcholine.

Thiophosphate containing analogs of phosphatidylcholine have been synthesized with varying degrees of structural complexity. These analogs have been used in a continuous spectrophotometric assay for phospholipase C from Clostridium perfringens in order to examine the requirement for substrate ester functionalities and the stereoselectivity of the enzyme. The substrate analogs with ester groups in the nonpolar portion of the molecule were acceptable substrates for phospholipase C, while those analogs without ester functionalities were not hydrolyzed. Substrate analogs with chiral centers were resolved using the stereospecificity of phospholipase A2 from Crotalus atrox venom. These resolved substrates were used to study the biphasic hydrolytic time courses observed when rac-dioctanoylphosphatidylthiocholine was used as substrate. The "naturally occurring" enantiomer with R absolute configuration was rapidly hydrolyzed in the presence of phospholipase C while the "nonnaturally occurring" enantiomer with S configuration was slowly hydrolyzed only after a long induction or "lag" period. The selectivity for the R enantiomer over the S enantiomer can be lessened by altering the composition of the substrate micelles resulting in accelerated rates of hydrolysis of the S enantiomer.

ESR parameters for cupric bleomycin in the mobilized state.

The configuration of the copper complex of the glycopeptide bleomycin, CuBlm, is presumed to be pyramidal square planar from a previous X-ray structural determination of a fragment of cupric bleomycin. This study presents evidence for a difference in the ESR parameters for cupric bleomycin in the liquid as opposed to the solid state. A decrease in Aiso for CuBlm in the liquid state can be directly surmised from the low frequency S-band spectrum for which three of the four cupric hyperfine lines are partially resolved. Computer simulated spectra infer that the absolute value of All increases about 100 MHz and the value of Al may change sign for CuBlm in the liquid state. Simulations using a rotational correlation time of about 250 psec. indicate that CuBLM may not be spherical in the liquid phase. The fastest component for anisotropic motion could dominate and account for the well resolved cupric hyperfine structure. Furthermore, it is argued from an analysis of the cupric hyperfine coupling constants that the CuBlm structure opens up at room temperature and that the cupric ion is displaced from the square plane.