Steven Dymarkowski

Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans

1 We investigated the effect of oral creatine supplementation during leg immobilization and rehabilitation on muscle volume and function, and on myogenic transcription factor expression in human subjects. 2 A double‐blind trial was performed in young healthy volunteers (n=22). A cast was used to immobilize the right leg for 2 weeks. Thereafter the subjects participated in a knee‐extension rehabilitation programme (3 sessions week−1, 10 weeks). Half of the subjects received creatine monohydrate (CR; from 20 g down to 5 g daily), whilst the others ingested placebo (P; maltodextrin). 3 Before and after immobilization, and after 3 and 10 weeks of rehabilitation training, the cross‐sectional area (CSA) of the quadriceps muscle was assessed by NMR imaging. In addition, an isokinetic dynamometer was used to measure maximal knee‐extension power (Wmax), and needle biopsy samples taken from the vastus lateralis muscle were examined to asses expression of the myogenic transcription factors MyoD, myogenin, Myf5, and MRF4, and muscle fibre diameters. 4 Immobilization decreased quadriceps muscle CSA (∼10 %) and Wmax (∼25 %) by the same magnitude in both groups. During rehabilitation, CSA and Wmax recovered at a faster rate in CR than in P (P < 0.05 for both parameters). Immobilization changed myogenic factor protein expression in neither P nor CR. However, after rehabilitation myogenin protein expression was increased in P but not in CR (P < 0.05), whilst MRF4 protein expression was increased in CR but not in P (P < 0.05). In addition, the change in MRF4 expression was correlated with the change in mean muscle fibre diameter (r=0.73, P < 0.05). 5 It is concluded that oral creatine supplementation stimulates muscle hypertrophy during rehabilitative strength training. This effect may be mediated by a creatine‐induced change in MRF4 and myogenin expression.

Remodeling of T-Tubules and Reduced Synchrony of Ca2+ Release in Myocytes From Chronically Ischemic Myocardium

In ventricular cardiac myocytes, T-tubule density is an important determinant of the synchrony of sarcoplasmic reticulum (SR) Ca2+ release and could be involved in the reduced SR Ca2+ release in ischemic cardiomyopathy. We therefore investigated T-tubule density and properties of SR Ca2+ release in pigs, 6 weeks after inducing severe stenosis of the circumflex coronary artery (91±3%, N=13) with myocardial infarction (8.8±2.0% of total left ventricular mass). Severe dysfunction in the infarct and adjacent myocardium was documented by magnetic resonance and Doppler myocardial velocity imaging. Myocytes isolated from the adjacent myocardium were compared with myocytes from the same region in weight-matched control pigs. T-tubule density quantified from the di-8-ANEPPS (di-8-butyl-amino-naphthyl-ethylene-pyridinium-propyl-sulfonate) sarcolemmal staining was decreased by 27±7% (P<0.05). Synchrony of SR Ca2+ release (confocal line scan images during whole-cell voltage clamp) was reduced in myocardium myocytes. Delayed release (ie, half-maximal [Ca2+]i occurring later than 20 ms) occurred at 35.5±6.4% of the scan line in myocardial infarction versus 22.7±2.5% in control pigs (P<0.05), prolonging the time to peak of the line-averaged [Ca2+]i transient (121±9 versus 102±5 ms in control pigs, P<0.05). Delayed release colocalized with regions of T-tubule rarefaction and could not be suppressed by activation of protein kinase A. The whole-cell averaged [Ca2+]i transient amplitude was reduced, whereas L-type Ca2+ current density was unchanged and SR content was increased, indicating a reduction in the gain of Ca2+-induced Ca2+ release. In conclusion, reduced T-tubule density during ischemic remodeling is associated with reduced synchrony of Ca2+ release and reduced efficiency of coupling Ca2+ influx to Ca2+ release.

Implications of SENSE MR in routine clinical practice

Sensitivity encoding (SENSE) uses multiple MRI receive coil elements to encode spatial information in addition to traditional gradient encoding. Requiring less gradient encodings translates into shorter scan times, which is extremely beneficial in many clinical applications. SENSE is available to routine diagnostic imaging for the past 2 years. This paper highlights the use of SENSE with scan time reduction factors up to 6 in contrast-enhanced MRA, routine abdominal imaging, mammography, cardiac and neuro imaging. It is shown that SENSE has opened new horizons in both routine and advanced MR imaging.

Respiration-induced movement of the upper abdominal organs: a pitfall for the three-dimensional conformal radiation treatment of pancreatic cancer.

Respiration-induced movement of the upper abdominal organs (pancreas, liver and kidneys) was assessed in 12 subjects using dynamic magnetic resonance imaging. The movement of each organ in the cranio-caudal, the lateral and the anterior-posterior direction was deduced from the movement of the center of gravity on two-dimensional images. This center of gravity was computed from the volume delineated on sequential 8-mm slices of both sagittal and coronal dynamic series. The largest movements were noticed in the cranio-caudal direction for pancreas and liver (23.7+/-15.9 mm and 24.4+/-16.4 mm). The kidneys showed smaller movements in the cranio-caudal direction (left kidney 16.9+/-6.7 mm and right kidney 16.1+/-7.9 mm). The movements of the different organs in the anterior-posterior and lateral directions were less pronounced. It is of the greatest importance to be aware of these movements in the planning of a conformal radiation treatment for pancreatic cancer.

The value of fast MR imaging as an adjunct to ultrasound in prenatal diagnosis

Abstract.The aim of this study was to evaluate the role of MR imaging of the fetus to improve sonographic prenatal diagnosis of congenital anomalies. In 40 fetuses (not consecutive cases) with an abnormality diagnosed with ultrasound, additional MR imaging was performed. The basic sequence was a T2-weighted single-shot half Fourier (HASTE) technique. Head, neck, spinal, thoracic, urogenital, and abdominal fetal pathologies were found. This retrospective, observational study compared MR imaging findings with ultrasonographic findings regarding detection, topography, and etiology of the pathology. The MR findings were evaluated as superior, equal to, or inferior compared with US, in consent with the referring gynecologists. The role of these findings in relation to pregnancy management was studied and compared with postnatal follow-up in 30 of 40 babies. Fetal MRI technique was successful in 36 of 39 examinations and provided additional information in 21 of 40 fetuses (one twin pregnancy with two members to evaluate). More precise anatomy and location of fetal pathology (20 of 40 cases) and additional etiologic information (8 of 40 cases) were substantial advantages in cerebrospinal abnormalities [ventriculomegaly, encephalocele, vein of Galen malformation, callosal malformations, meningo(myelo)cele], in retroperitoneal abnormalities (lymphangioma, renal agenesis, multicystic renal dysplasia), and in neck/thoracic pathology [cervical cystic teratoma, congenital hernia diaphragmatica, congenital cystic adenomatoid lung malformation (CCAM)]. This improved parental counseling and pregnancy management in 15 pregnancies. In 3 cases, prenatal MRI findings did not correlate with prenatal ultrasonographic findings or neonatal diagnosis. The MRI provided a more detailed description and insight into fetal anatomy, pathology, and etiology in the vast majority of these selected cases. This improved prenatal parental counseling and postnatal therapeutic planning.

Quantification of Myocardial Area at Risk With T2-Weighted CMR Comparison With Contrast-Enhanced CMR and Coronary Angiography

OBJECTIVES We sought to quantify the myocardium at risk in reperfused acute myocardial infarction (AMI) in man with T2-weighted (T2W) cardiac magnetic resonance (CMR). BACKGROUND The myocardial area at risk (AAR) is defined as the myocardial tissue within the perfusion bed distally to the culprit lesion of the infarct-related coronary artery. T2W CMR is appealing to retrospectively determine the myocardial AAR after reperfused AMI. Data on the utility of this technique in humans are limited. METHODS One hundred eight patients with successfully reperfused ST-segment elevation AMI were studied between 1 and 20 days after percutaneous coronary intervention (PCI). We compared the volume of hyperintense myocardium on T2W CMR with the myocardial AAR determined by contrast-enhanced CMR with infarct endocardial surface length (ESL) and AAR estimated by conventional coronary angiography with the BARI (Bypass Angioplasty Revascularization Investigation) risk score. RESULTS The volume of hyperintense myocardium on T2W CMR (mean 32 +/- 16%, range 3% to 67%) was consistently larger than the volume of myocardial infarction measured with contrast-enhanced images (mean 17 +/- 12%, range 0% to 55%) (p < 0.001). Myocardial salvage ranged from -4% to 45% of the left ventricular myocardium (mean 14 +/- 10%). The AAR determined by T2W CMR compared favorably with the infarct ESL (r = 0.77) with contrast-enhanced CMR, and there was moderate correlation between the BARI angiographic risk score and infarct ESL (r = 0.42). The time between PCI and CMR did not cause a significant difference in the volume of T2W hyperintense myocardium (r = 0.11, p = 0.27) or the calculated volume of salvaged myocardium (r = 0.12, p = 0.23). CONCLUSIONS T2W CMR performed early after successfully reperfused AMI in humans enables retrospective quantification of the myocardial AAR and salvaged myocardium.

Cardiac Three-Dimensional Magnetic Resonance Imaging and Fluoroscopy Merging A New Approach for Electroanatomic Mapping to Assist Catheter Ablation

Background— Modern nonfluoroscopic mapping systems construct 3D electroanatomic maps by tracking intracardiac catheters. They require specialized catheters and/or dedicated hardware. We developed a new method for electroanatomic mapping by merging detailed 3D models of the endocardial cavities with fluoroscopic images without the need for specialized hardware. This developmental work focused on the right atrium because of the difficulties in visualizing its anatomic landmarks in 3D with current approaches. Methods and Results— Cardiac MRI images were acquired in 39 patients referred for radiofrequency catheter ablation using balanced steady state free-precession sequences. We optimized acquisition and developed software for construction of detailed 3D models, after contouring of endocardial cavities with cross-checking of different imaging planes. 3D models were then merged with biplane fluoroscopic images by methods for image calibration and registration implemented in a custom software application. The feasibility and accuracy of this merging process were determined in heart-cast experiments and electroanatomic mapping in patients. Right atrial dimensions and relevant anatomic landmarks could be identified and measured in all 3D models. Cephalocaudal, posteroanterior, and lateroseptal diameters were, respectively, 65±11, 54±11, and 57±9 mm; posterior isthmus length was 26±6 mm; Eustachian valve height was 5±5 mm; and coronary sinus ostium height and width were 16±3 and 12±3 mm, respectively (n=39). The average alignment error was 0.2±0.3 mm in heart casts (n=40) and 1.9 to 2.5 mm in patient experiments (n=9), ie, acceptable for clinical use. In 11 patients, reliable catheter positioning and projection of activation times resulted in 3D electroanatomic maps with an unprecedented level of anatomic detail, which assisted ablation. Conclusions— This new approach allows activation visualization in a highly detailed 3D anatomic environment without the need for a specialized nonfluoroscopic mapping system.

Clinical cardiac MRI

Cardiac MR Physics.- MR Contrast Agents for Cardiac Imaging.- Practical Setup.- Cardiac Anatomy.- Cardiovascular MR Imaging Planes and Segmentation.- Cardiac Function.- Myocardial Perfusion.- Ischemic Heart Disease.- Nonischemic Myocardial Disease.- Pulmonary Hypertension.- Heart Failure and Heart Transplantation.- Pericardial Disease.- Cardiac Masses.- Valvular Heart Disease.- Coronary Artery Disease.- Congenital Heart Disease.- Great Vessels.- MR-Guided Cardiac Catheterization.- Cardiac Modelling.- Future Perspectives.- General Conclusion.

High dose intracoronary adenosine for myocardial salvage in patients with acute ST-segment elevation myocardial infarction

AIMS Previous studies have suggested that intravenous administration of adenosine improves myocardial reperfusion and reduces infarct size in ST-elevation myocardial infarction (STEMI) patients. Intracoronary administration of adenosine has shown conflicting results. METHODS AND RESULTS In a prospective, single-centre, double-blind, placebo-controlled clinical study, we assessed whether selective intracoronary administration of adenosine distal to the occlusion site immediately before initial balloon inflation results in myocardial salvage and decreased microvascular obstruction (MVO) as assessed with cardiac magnetic resonance imaging (MRI). Using a combination of T(2)-weighted and contrast-enhanced sequences, myocardial salvage index (MSI) was defined as the percentage of the area at risk that did not become necrotic. We randomized 112 patients presenting with STEMI within 12 h from symptom onset to selective intracoronary administration of adenosine 4 mg or matching placebo. In 100/110 (91%) patients receiving study drug, MRI was performed on Days 2-3. No significant difference in MSI was found between adenosine- and placebo-treated patients: 41.3% (20.8, 66.7) vs. 47.8% (39.8, 60.9) [median (Q1, Q3)] (P = 0.52). The extent of MVO was comparable in both groups, with a trend favouring the placebo group: 2.4 g (0.0, 6.8) vs. 5.9 g (0.0, 12.8) after adenosine (P = 0.07). TIMI flow grade, TIMI frame count, myocardial blush grade, and ST-segment resolution after primary percutaneous coronary intervention were similar between groups. After 4 months, infarct size was similar in both treatment groups. CONCLUSION We found no evidence that selective high-dose intracoronary administration of adenosine distal to the occlusion site of the culprit lesion in STEMI patients results in incremental myocardial salvage or a decrease in microvascular obstruction.

Patient acceptance for CT colonography: what is the real issue?

Abstract. The aim of this study was to evaluate the discomfort associated with CT colonography compared with colonoscopy and bowel purgation cleansing, and to evaluate patient preference between CT colonography and colonoscopy. In a total of 124 patients, scheduled for multidetector virtual CT colonography and diagnostic colonoscopy, patient acceptance and future preference were assessed during the different steps of the procedure (colon preparation, CT examination, and conventional colonoscopy). Patients who described contradictory findings between the degree of discomfort and their preference regarding follow-up examinations were retrospectively reinterviewed regarding the reason for this discrepancy. Colonoscopy was graded slightly more uncomfortable than virtual CT colonography, but the preparation was clearly the most uncomfortable part of the procedure. Concerning their preference regarding follow-up examinations, 71% of the patients preferred virtual CT colonography, 24% preferred colonoscopy, and 5% had no preference. Twenty-eight percent of the patients preferred virtual CT colonography despite that they thought it was equally or even more uncomfortable than colonoscopy. This was mainly due to the faster procedure (17 patients), the lower physical challenge (14 patients), and the lack of sedation (12 patients) of virtual CT colonography. Factors other than the discomfort related to the examinations play an important role in the patients preference for virtual CT colonography, namely the faster procedure, the lower physical challenge, and the lack of sedation. Since the preparation plays a major decisive factor in the patient acceptance of virtual CT colonography, more attention should be given to fecal tagging.