Parallel transmit excitation at 1.5 T based on the minimization of a driving function for device heating.

PURPOSE: To provide a rapid method to reduce the radiofrequency (RF) E-field coupling and consequent heating in long conductors in an interventional MRI (iMRI) setup. METHODS: A driving function for device heating (W) was defined as the integration of the E-field along the direction of the wire and calculated through a quasistatic approximation. Based on this function, the phases of four independently controlled transmit channels were dynamically changed in a 1.5 T MRI scanner. During the different excitation configurations, the RF induced heating in a nitinol wire immersed in a saline phantom was measured by fiber-optic temperature sensing. Additionally, a minimization of W as a function of phase and amplitude values of the different channels and constrained by the homogeneity of the RF excitation field (B1) over a region of interest was proposed and its results tested on the benchtop. To analyze the validity of the proposed method, using a model of the array and phantom setup tested in the scanner, RF fields and SAR maps were calculated through finite-difference time-domain (FDTD) simulations. In addition to phantom experiments, RF induced heating of an active guidewire inserted in a swine was also evaluated. RESULTS: In the phantom experiment, heating at the tip of the device was reduced by 92% when replacing the body coil by an optimized parallel transmit excitation with same nominal flip angle. In the benchtop, up to 90% heating reduction was measured when implementing the constrained minimization algorithm with the additional degree of freedom given by independent amplitude control. The computation of the optimum phase and amplitude values was executed in just 12 s using a standard CPU. The results of the FDTD simulations showed similar trend of the local SAR at the tip of the wire and measured temperature as well as to a quadratic function of W, confirming the validity of the quasistatic approach for the presented problem at 64 MHz. Imaging and heating reduction of the guidewire were successfully performed in vivo with the proposed hardware and phase control. CONCLUSIONS: Phantom and in vivo data demonstrated that additional degrees of freedom in a parallel transmission system can be used to control RF induced heating in long conductors. A novel constrained optimization approach to reduce device heating was also presented that can be run in just few seconds and therefore could be added to an iMRI protocol to improve RF safety.

Variability in diagnosing Creutzfeldt-Jakob disease using standard and proposed diagnostic criteria.

INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive dementia with a median survival of 2-14 months. The diagnosis can only be made accurately by biopsy/autopsy. However, this is not always feasible or desirable. Thus, diagnostic criteria have been proposed by UCSF, European MRI-CJD Consortium, and WHO. We will compare these criteria. PATIENTS AND METHODS: Retrospective study of 31 patients (average age of 69.2 years) between 2003 to 2010 by ICD9 codes 046.1, 046.11, and 046.19. RESULTS: All patients presented with rapidly progressive dementia (mean duration of 4.25 months). Pyramidal and extrapyramidal findings, myoclonus, cerebellar changes, akinetic mutism, and visual disturbances were observed in 6.5-48.4%. Five had periodic pattern on EEG. CSF biomarker 14-3-3 was positive in 11. Tau was positive in 6. Neuron specific enolase was positive in 9. By consensus (kappa = 0.62), MRI was "typical" of CJD in 23 with cortical ribboning (n = 16), basal ganglia hyperintensity (n = 15), or combination (n = 8). By WHO criteria, which does not include neuroimaging, CJD was diagnosed in 10, but 14 if any CSF biomarker was used (p = NS). The UCSF criteria, which does not include CSF biomarkers, diagnosed 18 cases, and the European MRI-CJD Consortium, which includes neuroimaging and CSF biomarkers but with less neurological signs, diagnosed 23 cases (p < 0.05 and p < 0.001, respectively). CJD-mimics included urosepsis, neurosarcoidosis, idiopathic left temporal lobe epilepsy, alcohol intoxication, central nervous system vasculitis, viral encephalitis, and non-Hodgkin's lymphoma. CONCLUSION: This study illustrates the variability in diagnosing CJD and emphasizes the diagnostic utility of neuroimaging. It also highlights false-positives that occur with neuroimaging.

MRI roadmap-guided transendocardial delivery of exon-skipping recombinant adeno-associated virus restores dystrophin expression in a canine model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) cardiomyopathy patients currently have no therapeutic options. We evaluated catheter-based transendocardial delivery of a recombinant adeno-associated virus (rAAV) expressing a small nuclear U7 RNA (U7smOPT) complementary to specific cis-acting splicing signals. Eliminating specific exons restores the open reading frame resulting in translation of truncated dystrophin protein. To test this approach in a clinically relevant DMD model, golden retriever muscular dystrophy (GRMD) dogs received serotype 6 rAAV-U7smOPT via the intracoronary or transendocardial route. Transendocardial injections were administered with an injection-tipped catheter and fluoroscopic guidance using X-ray fused with magnetic resonance imaging (XFM) roadmaps. Three months after treatment, tissues were analyzed for DNA, RNA, dystrophin protein, and histology. Whereas intracoronary delivery did not result in effective transduction, transendocardial injections, XFM guidance, enabled 30±10 non-overlapping injections per animal. Vector DNA was detectable in all samples tested and ranged from <1 to >3000 vector genome copies per cell. RNA analysis, western blot analysis, and immunohistology demonstrated extensive expression of skipped RNA and dystrophin protein in the treated myocardium. Left ventricular function remained unchanged over a 3-month follow-up. These results demonstrated that effective transendocardial delivery of rAAV-U7smOPT was achieved using XFM. This approach restores an open reading frame for dystrophin in affected dogs and has potential clinical utility.

Real-time magnetic resonance imaging to guide pediatric endovascular procedures.

Although x-ray fluoroscopy (XRF) has guided diagnostic and therapeutic transcatheter procedures for decades, certain limitations still exist. XRF still visualizes tissue poorly and relies on projection of shadows that do not convey depth information. Adjunctive echocardiography overcomes some of these limitations but still suffers suboptimal or unreliable imaging windows. Furthermore, ionizing radiation exposure in children imparts a cancer risk. An interventional platform using real-time magnetic resonance imaging (MRI) may offer superior image guidance without radiation. Although there are many remaining challenges, but real-time MRI has the potential to revolutionize transcatheter therapeutics.

Delivery and tracking of therapeutic cell preparations for clinical cardiovascular applications.

Experimental observations suggesting adult stem cell plasticity and cross-lineage transdifferentiation have underpinned the investigation of cell therapy for cardiovascular disease. Many challenges still face the full realization of cardiovascular regenerative medicine. This brief review will highlight some of these, with emphasis on the choice of cell preparation, route of cell delivery and tracking of delivered cells.

West Nile virus infection: a new acute paralytic illness.

OBJECTIVE: To determine the clinical, laboratory, electrodiagnostic, radiologic, and pathologic characteristics that define the spectrum of CNS disease caused by West Nile virus (WNV) infection. METHODS: The records of all patients hospitalized at the Cleveland Clinic from August 2002 to September 2002 with WNV infection were reviewed. RESULTS: Of 23 cases, the median age was 74 years old, and 74% were men. Symptoms included fever (100%), altered mental status (74%), gastrointestinal complaints (43%), back pain (35%), and rash (26%). In half, meningitis or encephalitis overlapped with flaccid weakness that progressed over 3 to 8 days, with a tendency to be proximal and asymmetric. Laboratory abnormalities included hyponatremia (30%) and initial CSF neutrophilic pleocytosis. Electrodiagnostic studies in two patients showed reduced motor amplitudes with normal conduction velocities and active denervation. In two other patients, reduced sensory amplitudes were also seen. MRI changes included cauda equina enhancement and parenchymal spinal cord signal abnormalities and parenchymal or leptomeningeal signal changes in the brain. Autopsy in three cases showed chronic perivascular inflammation in the brain and inflammatory changes with anterior horn cell loss in the spinal cord. CONCLUSION: An overlapping spectrum of meningitis, encephalitis, and myeloradiculitis occurs in CNS WNV infection. Fever, rash, abdominal and back pain, preceding a proximal, asymmetric flaccid weakness, with CSF pleocytosis help distinguish the motor syndrome from Guillain-Barré syndrome. Pathologic changes in the CNS resembled poliomyelitis.

Primary renal artery stenting: characteristics and outcomes after 363 procedures.

BACKGROUND: Stenting improves the acute results of percutaneous balloon angioplasty for atherosclerotic renal artery stenosis. Predictors of benefit and angiographic restenosis are not well understood. We describe the technical and clinical success of renal artery stenting in a large consecutive series of patients with hypertension or renal insufficiency. We identify clinical, procedural, and anatomic factors that might influence outcome, restenosis, and survival. METHODS: Primary renal artery stenting was performed in 300 consecutive patients who underwent 363 stent procedures in 358 arteries. Angiograms were analyzed quantitatively. Clinical and angiographic follow-up data are available after a median of 16.0 months. RESULTS: At baseline, 87% of patients had hypertension, and 37% had chronic renal insufficiency. The mean age was 70 years (interquartile range 63.1-74.6) years. The stenosis was unilateral in 49% and bilateral in 48% and involved a solitary functioning kidney in 3.6%. The stenting procedure was successful in all attempts. There were no procedural deaths or emergency renal surgical procedures. Postprocedure azotemia was seen in 45 of 363 (12%) procedures but persisted in only 6 patients (2%), all of whom had baseline renal insufficiency. Systolic and diastolic blood pressures were significantly reduced (systolic blood pressure from 164.0 +/- 28.7 to 142.4 +/- 19.1 mm Hg, P <.001). At follow-up, 70% of patients had improved blood pressure control regardless of renal function. In patients with baseline renal insufficiency, 19% had improvement in serum creatinine levels at follow-up, 54% had stabilization, and 27% had deterioration. Follow-up mortality was 10% and was predicted by baseline creatinine levels (odds ratio 1.72 for each 1 mg/dL creatinine increment, 95% confidence interval 1.13-2.49) and extent of coronary artery disease (odds ratio 1.66 for each diseased coronary artery, 95% confidence interval 1.03-2.67). Angiographic restenosis was found in 21% of 102 patients overall and was less common (12%) in arteries with a reference caliber >4.5 mm (P <.01 vs caliber <4.5 mm). Neither poststenotic dilation nor severity of angiographic stenosis predicted clinical outcome. CONCLUSIONS: Primary renal artery stenting can be performed safely with nearly uniform technical success. The majority of patients with hypertension or renal insufficiency derive benefit. Follow-up mortality is 5-fold higher in patients with baseline renal insufficiency. Clinical and angiographic features did not predict blood pressure or renal functional outcome. Restenosis is more common in renal arteries with a reference caliber less than 4.5 mm.

Design of the therapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (TRAFFIC) trial.

The Therapeutic Angiogenesis With Recombinant Fibroblast Growth Factor-2 for Intermittent Claudication (TRAFFIC) is a large, randomized, placebo-controlled, regimen-finding trial of intra-arterial recombinant fibroblast growth factor-2 in patients with intermittent claudication. This report describes the major design considerations and end points in TRAFFIC.

Detection of atherosclerosis using a novel positron-sensitive probe and 18-fluorodeoxyglucose (FDG).

Inflammation contributes to atherosclerotic plaque remodeling, enlargement and rupture. Non-invasive imaging of coronary artery inflammation could help target therapy to 'vulnerable' atheromata, but is limited because of small tissue mass and arterial motion. Local radiopharmaceutical imaging may overcome some of these limitations. We used a positron-sensitive fiberoptic probe, which can distinguish positron emissions from annihilation photons, to identify diseased from healthy endothelium in an atherosclerotic model. New Zealand White rabbits underwent Fogarty-catheter injury of an iliac artery and then were fed a high-fat diet for 3 weeks. Fasted animals received 90-180 MBq of 18-fluorodeoxyglucose (FDG) 2-4 h before sacrifice and harvest of injured and uninjured iliacs. Arteries were incised longitudinally and the probe was placed in contact with the arterial intima. Multiple measurements were obtained along 1 cm artery segments in 60 s intervals, and corrected for 18F decay and background. Measurements were recorded over 93 injured and normal artery segments in 11 animals. Mean probe Z-scores were 4.8-fold higher (CI 3.4-6.3) over injury atherosclerosis compared with uninjured normal iliac artery segments (P<0.001). Gamma counting confirmed that injured artery segments accumulated more FDG per gram than did normal segments (0.203% x kg injected dose per gram of tissue versus 0.042, P<0.001). Non-arterial tissue also accumulated FDG avidly, particularly reticuloendothelial tissues and blood. Delayed sacrifice, 4 h compared with 2 h after animal FDG injection, further reduced blood background counts and improved the signal-to-noise ratio. Histopathology confirmed that injured iliac artery had significantly higher intimal and medial cross-sectional area compared with uninjured artery. Injured artery also had significantly higher macrophage and smooth muscle cell density. Positron-sensitive probe counts correlated with the intima to media ratio (r =0.63, P = 0.03). Our positron-sensitive probe distinguishes atherosclerotic from healthy artery in a blood-free field. Intravascular study of plaque biology may be feasible using FDG and a positron-sensitive probe.

Blood speed imaging with an intraluminal array.

In applications in which Doppler processing is not possible, such as side-looking intravascular imaging systems, decorrelation methods can be used to estimate blood speed. Here, a method is presented measuring relative blood speed using an FIR filter bank to estimate temporal decorrelation rates. It can be implemented in a modern commercially available ultrasound imaging system with no additional hardware. Both simulations and experiments using an intraluminal scanner appropriate for coronary artery applications have tested the system. In this study, the FIR filter bank is contrasted with previous methods, and its utility is further demonstrated with real-time color flow images from a pig model.

Robert Schumann.

Robert Schumann, one of the giants of early romantic music, was born in Saxony in 1810 and died in an asylum shortly after his 46th birthday. Early in life, he demonstrated extraordinary skills in both music and journalism; he remained active in both areas until his final illness. His marriage to the remarkable pianist, Clara Wieck, provided him with both much-needed emotional support and a highly effective champion of his music throughout her lengthy career. Schumann's plans to be a concert pianist were thwarted at least partially by an injury to his right hand, the nature of which has been the subject of much speculation. After considering what few facts are available, the author concludes that this may have represented focal dystonia. His compositional output waxed and waned dramatically over his professional life, reflecting to some degree his emotional state. It is considered most likely that he suffered from a major affective disorder, bipolar type. This ultimately led to a suicide attempt in February 1854, and to his eventual death in July 1856. Despite wide-spread and reasonable suspicion that he may have died from neurosyphilis, severe malnutrition from self-starvation seems more likely.

Acute hemodynamic changes during carotid artery stenting.

To determine the clinical significance of acute hemodynamic disturbances during stenting in the carotid sinus region, we assessed the relation between intraprocedural changes in heart rate (HR) and blood pressure (BP) and adverse neurologic and cardiac outcomes. Eighteen patients underwent carotid stenting with the Wallstent (Schneider Inc). Suitable candidates had at least 60% diameter stenosis of the carotid artery by angiography. Initial and nadir HR and BP were recorded during the predilatation, stent delivery, and postdilatation periods. Bradycardia was defined as HR < or =60 beats/min and hypotension as systolic BP < or =100 mm Hg. Nineteen Wallstents were successfully deployed in all 19 carotid arteries. Some degree of bradycardia or hypotension occurred in 68% of carotid stent procedures, but administration of vasoactive medications was necessary in only 7 patients (37%) with more persistent hemodynamic disturbances. Hypotension or the need for continuous vasopressor therapy was significantly more common during postdilatation (32%) than in the predilatation period (5%) (p = 0.02). Bradycardia was not reduced by prophylactic atropine. In 1 patient the hemodynamic response to stenting may have contributed to an adverse neurologic and cardiac outcome. Thus, despite frequent fluctuations in HR and BP, most carotid stenting procedures were performed with excellent overall results, even in patients at high risk.

Kissing stents in the aortic bifurcation.

BACKGROUND: We report the first series of simultaneously delivered stents used to treat stenosis of the aortic bifurcation. Surgical treatment of aortoiliac occlusive disease carries up to a 3% mortality rate. Percutaneous balloon techniques to treat aortic bifurcation stenosis, although safer, are still associated with up to a 9% incidence of dissection, thrombosis, or significant residual stenosis. Kissing stent insertion should decrease the incidence of these complications. METHODS: Twenty patients underwent kissing stent insertion. Suitable candidates included patients with symptoms of lower limb ischemia and significant atherosclerotic lesions in both ostial common iliac arteries (n = 15) or with extremely complex single ostial iliac stenoses (n = 5). Palmaz stents were delivered simultaneously to both limbs of the aortic bifurcation. RESULTS: Kissing stent insertion was successfully performed in all 20 patients without acute complications. Mean percent stenosis decreased from 46.2%+/-24.8% to -6.8%+/-13.3% (P = .0001) in the right iliac artery, 42.3%+/-22.8% to -1.6% +/-18.1% (P = .0001) in the left iliac artery, and 19.1%+/-16.6% to 2.3%+/-16.4% (P= .0008) in the distal aorta. Intermittent claudication symptoms were improved in 18 (95%) of 19 patients with 12 (63%) of 19 patients becoming totally asymptomatic. The strongest predictor of clinical outcome after kissing stent insertion was the preprocedural extent of femoropopliteal disease: 8 (89%) of 9 patients with femoropopliteal narrowing <75% bilaterally became completely asymptomatic at follow-up compared with only 3 (30%) of 10 patients with more severe stenoses (P = .02). CONCLUSIONS: We have demonstrated in 20 patients that stenoses of the aortic bifurcation can be treated effectively with kissing stents with few serious adverse events.

Superimposed stents in the management of acute recoil after Palmaz-Schatz stenting.

We report a patient in whom aorto-ostial stenting with a Palmaz-Schatz coronary stent was complicated by significant acute elastic recoil, despite appropriate positioning of the stent and full expansion of a high-pressure, postdilatation balloon. Superimposing a Palmaz biliary stent overcame the inward radial force of this lesion and achieved an adequate lumen.

Postpartum neuralgic amyotrophy.

We report 11 women with at least one episode of neuralgic amyotrophy occurring postpartum. One woman had three episodes-two postpartum and a third occurring after minor foot surgery. Two others had a second episode, one following a first trimester spontaneous abortion and one after a viral syndrome. Pain followed delivery from as little as 1 to 2 hours to up to 2 weeks and usually lasted from a few weeks to several months. Weakness, if delayed, followed onset of pain by 2 or 3 days up to 5 weeks. Four of the episodes were bilateral. Clinical weakness and electrodiagnostic findings varied widely, from involvement of a single peripheral nerve (e.g., long thoracic, anterior interosseous) to multiple bilateral proximal and distal nerves. Functional recovery was excellent (90 to 100%) in 8 of the 10 with adequate follow-up, requiring as little as 2 weeks or up to 3 years. Two women have moderate persisting weakness (both bilateral) at 3 years and 2 years. Five patients went on to subsequent deliveries without recurrence of neuralgic amyotrophy. Only one of the 11 women had a history suggesting familial neuralgic amyotrophy, a disorder generally thought to be associated particularly with postpartum episodes. Although the etiology of postpartum neuralgic amyotrophy remains unknown, an immunologic mechanism is suspected. Focal demyelination may play a role in some, but clearly axonal degeneration is predominant in the majority.