Translational research: moving discovery to practice.

In the first week of October, I announced the launch of a national consortium that will transform how clinical and translational research is conducted; ultimately enabling researchers to provide new treatments more efficiently and quickly to patients. This new consortium, funded through Clinical and Translational Science Awards (CTSAs), begins with 12 academic health centers (AHCs) located throughout the nation. An additional 52 AHCs are receiving planning grants to help them prepare to apply for a CTSA.

Noninvasive assessment of myocardial stunning from short-term coronary occlusion using tagged magnetic resonance imaging.

Brief myocardial ischemia of less than 20 min duration, followed by reperfusion, is known to cause transient contractile dysfunction, often termed myocardial stunning. Tagged magnetic resonance imaging offers a noninvasive method that can be used to quantify this regional mechanical dysfunction in stunned myocardium. To this end, a closed-chest canine model of myocardial stunning was created by short-term (approximately 20-min) coronary occlusion, via inflation of an angioplasty balloon placed fluoroscopically in the left anterior descending (LAD) coronary, followed by reperfusion. Changes in myocardial strain before occlusion, during occlusion, and at 15 and 30 min after reperfusion were determined using repeated-measures analysis of variance. After instrumentation but before coronary occlusion, global reductions in myocardial strain were observed relative to animals that did not undergo coronary catheterization procedures. Declines of 46% and 49% in regional myocardial blood flow in the LAD and left circumflex bed, respectively, from preinstrumentation levels occurred due to coronary angiography and placement of a deflated angioplasty balloon in the LAD for 1 hr. During LAD occlusion, maximum myocardial shortening was significantly reduced in the anterior and anteroseptal regions of the left ventricular apex (i.e., ischemic region) but returned to baseline values by 30 min after reperfusion. No augmentation of myocardial function was observed in the nonischemic regions during occlusion or reperfusion. Thus, this noninvasive technique to evaluate myocardial ischemia demonstrated a graded response in myocardial function to ischemia and persistent regional dysfunction or "myocardial stunning" after short-term coronary occlusion.

Oxygenation in the rabbit myocardium: assessment with susceptibility-dependent MR imaging.

PURPOSE: To determine the feasibility of using hemoglobin (Hb) desaturation as an indicator of myocardial oxygenation. MATERIALS AND METHODS: High-resolution gradient-echo nuclear magnetic resonance (MR) images of isolated, blood-perfused rabbit hearts were obtained at various blood oxygenation levels. The hearts were perfused at 37 degrees C with a Langendorff apparatus modified for nuclear MR imaging. The perfusate contained bovine red blood cells in a cardioplegic solution that eliminated motion artifacts and minimized arteriovenous oxygenation differences. Hb saturation was varied (7%-100%) randomly. Perfusion pressure was continuously monitored, and blood samples were obtained. RESULTS: There was a substantial correlation between image signal intensity in the myocardium and Hb saturation in the blood, believed to be due to susceptibility effects of the paramagnetic species deoxyhemoglobin. CONCLUSION: Direct and noninvasive determination of regional Hb saturation with susceptibility-dependent MR imaging may provide information regarding regional myocardial O2 content.

Acute effects of increased intravascular volume and hypoxia on the pulmonary circulation: assessment with high-resolution CT.

High-resolution computed tomography (HRCT) was used to evaluate acute morphologic changes in the circulation of anesthetized miniature pigs (a) after volume loading and (b) after induction of hypoxia. Before and after each challenge, serial HRCT scans were obtained at a constant position in the caudal lobes of the lung. Scans were digitized and analyzed to determine the extent of changes in the cross-sectional area of vessels greater than 300 microns in diameter. Parenchymal background attenuation in anterior, middle, and posterior lung regions was used to assess volume changes in vessels less than 300 microns in diameter. Volume loading increased cross-sectional area by 25.2% +/- 4.3 in arteries and by 37.8% +/- 6.1 in veins and caused a gravity-dependent increase in parenchymal attenuation. Hypoxia decreased parenchymal attenuation, which was consistent with constriction of vessels smaller than 300 microns. Larger arteries and veins reacted heterogeneously. Vascular dilation during volume loading was predominantly passive, and hypoxia increased vascular tone throughout the circulation. HRCT represents a new in vivo approach to investigate vascular responses to various stimuli.

Assessment of pulmonary airway reactivity with high-resolution CT.

The evaluation of airway reactivity plays a central role in the diagnosis of bronchial hyperreactivity and asthma. The authors used high-resolution computed tomography (HRCT) to assess airway reactivity and compared the results with simultaneously performed measurements of airway pressure (Paw). Ten anesthetized and ventilated dogs were studied in a control state, after saline aerosol application, and after histamine aerosol challenge. In each condition, Paw was determined and HRCT was performed at functional residual capacity. On the HRCT scans, the cross-sectional areas of airway lumina were measured by using a computer edging process. After histamine challenge, HRCT demonstrated a decrease in airway areas of 43% +/- 2% (mean +/- standard error) from baseline (control) and Paw increased 99% +/- 18%. Surprisingly, saline aerosol challenge also resulted in a significant decrease in airway areas (26% +/- 3%) from control, while Paw measurements did not change significantly. Airway reactivity varied between dogs and within dogs. The authors conclude that HRCT can depict the site and degree of airway reactions and thus represents a new tool to assess airway reactivity in vivo.

Pulmonary carcinoid tumors: CT assessment.

Computed tomography assessment of 634 surgically proven solitary pulmonary nodules included 12 pulmonary carcinoid tumors. Five were central (involving or directly abutting the bronchial tree), and seven were peripheral (surrounded by parenchyma). Three central and one peripheral lesion had CT numbers indicative of focal calcifications, frequently in the periphery of the nodule. Nodule size ranged from 1.2 to 3 cm. Nine nodules were smooth and round, two were irregular and lobulated, and in one the entire peripheral contour was difficult to assess because of postobstructive atelectasis secondary to tumor occlusion of the bronchus. The calculated average CT number ranged from 80.5 to 179 HU.

Human heart: tagging with MR imaging--a method for noninvasive assessment of myocardial motion.

Specified regions of the myocardium can be labeled in magnetic resonance (MR) imaging to serve as markers during contraction. The technique is based on locally perturbing the magnetization of the myocardium with selective radio-frequency (RF) saturation of multiple, thin tag planes during diastole followed by conventional, orthogonal-plane imaging during systole. The technique was implemented on a 0.38-T imager and tested on phantoms and volunteers. In humans, tags could be seen 60-450 msec after RF saturation, thus permitting sampling of the entire contractile phase of the cardiac cycle. Tagged regions appear as hypointense stripes, and their patterns of displacement reflect intervening cardiac motion. In addition to simple translation and rotation, complex motions such as cardiac twist can be demonstrated. The effects of RF pulse angle, relaxation times, and heart rate on depiction of the tagged region are discussed.

The solitary pulmonary nodule. Assessment, diagnosis, and management.

We have presented a brief overview of an approach that has been very successful in our hands in the patient with an SPN. Even though the patient who has undergone a thoracotomy is full of gratitude to his physician when told that the resected lesion was benign and does not question the need for the thoracotomy, we have met equally happy and gratified patients when they were told that their lesion is benign be it after CT densitometry or needle biopsy. When properly performed, these techniques demand care and attention to detail much like the surgeon performing a delicate procedure. Without proper care, these procedures can in fact reflect negatively on the physician performing them and fall in disrepute. CT densitometry and transthoracic needle aspiration biopsy allow effective management of the patient with an SPN with prompt documentation of both malignant or benign lesions. With the proper application of these techniques, the majority of patients with benign disease will not need a thoracotomy for diagnosis with resultant benefits to the patient as well as to third-party payers.

Solitary pulmonary nodules: CT assessment.

Computed tomography (CT) was used to examine 634 solitary pulmonary nodules (SPNs). Each lesion was assessed as benign or indeterminate on the basis of CT criteria. Benign nodules made up 44% of all SPNs and 58% of the 431 that were 2 cm or less in diameter. All malignant SPNs were assessed as indeterminate, and adenocarcinoma (42%) was the most common primary malignancy. A total of 176 (63% of benign SPNs) were correctly assessed as benign by CT. Ninety SPNs assessed as diffusely calcified were not so identified by conventional tomography at outside institutions. An SPN can be reliably assessed by CT as benign if it exhibits high attenuation values, exceeding a critical level and distributed diffusely throughout a CT section through the center of the lesion and a well-defined edge. Although 38 of 283 (13.4%) primary lung cancers contained localized calcification, there was no significant overlap with the diffuse calcification of benign lesions. Central carcinoid tumors may contain focal ossification, but such lesions may be recognized by noting the proximity of larger bronchi. Assessment of SPNs by CT is most effective for lesions 2.0 cm or less in diameter. For larger lesions, the frequency of benign disease was decreased (14.3% of 203), as was the percentage of benign SPNs correctly assessed as benign by CT (37.9%).