Neuroradiological findings of trisomy 13 in a rare long-term survivor.

Patau syndrome remains a difficult diagnosis for parents and a challenging conversation for clinicians due to the overall poor prognosis. Previous population-based reports have documented the sobering life expectancies of these patients, with few surviving to 1 year of age. Despite the high mortality rate in infants born with trisomy 13, there are several reports of survival into late childhood and early adulthood. While clinical outcomes have been well documented, there has been a paucity of literature describing postnatal imaging findings in long-term survivors. We present a case report of a 2-year-old girl with trisomy 13 who underwent brain magnetic resonance imaging examination at our institution to evaluate for possible structural abnormalities contributing to central sleep apnea. We describe the clinical and postnatal neuroimaging findings of this rare patient with trisomy 13. Understanding the spectrum of neuroradiological findings in long-term survivors with trisomy 13, in combination with other organ system abnormalities, could add important clinical information and help better predict patient outcomes and expectations among parents.

Determination of cryothermal injury thresholds in tissues impacted by cardiac cryoablation.

Despite widespread clinical use of cryoablation, there remain questions regarding dosing and treatment times which may affect efficacy and collateral injury. Dosing and treatment times are directly related to the degree of cooling necessary for effective lesion formation. Human and swine atrial, ventricular, and lung tissues were ablated using two cryoablation systems with concurrent infrared thermography. Post freeze-thaw samples were cultured and stained to differentiate viable and non-viable tissue. Matlab code correlated viability staining to applied freeze-thaw thermal cycles, to determine injury thresholds. Tissue regions were classified as live, injured, or dead based upon staining intensity at the lesion margin. Injury begins at rates of ∼10 °C/min to 0 °C, with non-viable tissue requiring cooling rates close to 100 °C/min to âˆ¼ -22 °C for swine and significantly greater cooling to -26 °C for human tissue (p = 0.041). At similar rates, lung tissue injury began at 0 °C, with human tissue requiring significantly less cooling, to âˆ¼ -15 °C for complete necrosis and -26 °C for swine (p = 0.024). Data suggest that there are no significant differences between swine and human myocardial response, but there may be differences between swine and human lung cryothermal tolerance.

The novel in vitro reanimation of isolated human and large mammalian heart-lung blocs.

BACKGROUND: In vitro isolated heart preparations are valuable tools for the study of cardiac anatomy and physiology, as well as for preclinical device testing. Such preparations afford investigators a high level of hemodynamic control, independent of host or systemic interactions. Here we hypothesize that recovered human and swine heart-lung blocs can be reanimated using a clear perfusate and elicit viable cardiodynamic and pulmonic function. Further, this approach will facilitate multimodal imaging, which is particularly valuable for the study of both functional anatomy and device-tissue interactions. Five human and 18 swine heart-lung preparations were procured using techniques analogous to those for cardiac transplant. Specimens were then rewarmed and reperfused using modifications of a closed circuit, isolated, beating and ventilated heart-lung preparation. Positive pressure mechanical ventilation was also employed, and epicardial defibrillation was applied to elicit native cardiac sinus rhythm. Videoscopy, fluoroscopy, ultrasound, and infrared imaging were performed for anatomical and experimental study. RESULTS: Systolic and diastolic left ventricular pressures observed for human and swine specimens were 68/2 ± 11/7 and 74/3 ± 17/5 mmHg, respectively, with associated native heart rates of 80 ± 7 and 96 ± 16 beats per minute. High-resolution imaging within functioning human pulmonary vasculature was obtained among other anatomies of interest. Note that one human specimen elicited poor cardiac performance post defibrillation. CONCLUSIONS: We report the first dynamic videoscopic images of the pulmonary vasculature during viable cardiopulmonary function in isolated reanimated heart-lung blocs. This experimental approach provides unique in vitro opportunities for the study of novel medical therapeutics applied to large mammalian, including human, heart-lung specimens.

MRI Reconstructions of Human Phrenic Nerve Anatomy and Computational Modeling of Cryoballoon Ablative Therapy.

The primary goal of this computational modeling study was to better quantify the relative distance of the phrenic nerves to areas where cryoballoon ablations may be applied within the left atria. Phrenic nerve injury can be a significant complication of applied ablative therapies for treatment of drug refractory atrial fibrillation. To date, published reports suggest that such injuries may occur more frequently in cryoballoon ablations than in radiofrequency therapies. Ten human heart-lung blocs were prepared in an end-diastolic state, scanned with MRI, and analyzed using Mimics software as a means to make anatomical measurements. Next, generated computer models of ArticFront cryoballoons (23, 28 mm) were mated with reconstructed pulmonary vein ostias to determine relative distances between the phrenic nerves and projected balloon placements, simulating pulmonary vein isolation. The effects of deep seating balloons were also investigated. Interestingly, the relative anatomical differences in placement of 23 and 28 mm cryoballoons were quite small, e.g., the determined difference between mid spline distance to the phrenic nerves between the two cryoballoon sizes was only 1.7 ± 1.2 mm. Furthermore, the right phrenic nerves were commonly closer to the pulmonary veins than the left, and surprisingly tips of balloons were further from the nerves, yet balloon size choice did not significantly alter calculated distance to the nerves. Such computational modeling is considered as a useful tool for both clinicians and device designers to better understand these associated anatomies that, in turn, may lead to optimization of therapeutic treatments.

Intraosseous Hemangioma of the Middle Turbinate: A Case Report of a Rare Entity and Literature Review.

Intraosseous hemangiomas arising from the nasal turbinate are exceedingly rare, with few reported cases in the literature. We describe a 61-year-old man found to have a nasal cavity mass on sinus computed tomograph (CT) and magnetic resonance imaging (MRI). Although an atypical site of occurrence, distinctive internal honeycomb bony trabeculations demonstrated on CT allowed the correct diagnosis of an intraosseous hemangioma to be prospectively proposed by the interpreting radiologist which had direct clinical and surgical impacts.

Left phrenic nerve anatomy relative to the coronary venous system: Implications for phrenic nerve stimulation during cardiac resynchronization therapy.

The objective of this study was to quantitatively characterize anatomy of the human phrenic nerve in relation to the coronary venous system, to reduce undesired phrenic nerve stimulation during left-sided lead implantations. We obtained CT scans while injecting contrast into coronary veins of 15 perfusion-fixed human heart-lung blocs. A radiopaque wire was glued to the phrenic nerve under CT, then we created three-dimensional models of anatomy and measured anatomical parameters. The left phrenic nerve typically coursed over the basal region of the anterior interventricular vein, mid region of left marginal veins, and apical region of inferior and middle cardiac veins. There was large variation associated with the average angle between nerve and veins. Average angle across all coronary sinus tributaries was fairly consistent (101.3°-111.1°). The phrenic nerve coursed closest to the middle cardiac vein and left marginal veins. The phrenic nerve overlapped a left marginal vein in >50% of specimens.

In vitro assessment of induced phrenic nerve cryothermal injury.

BACKGROUND: Phrenic nerve injury, both left and right, is considered a significant complication of cryoballoon ablation for treatment of drug-refractory atrial fibrillation, and functional recovery of the phrenic nerve can take anywhere from hours to months. OBJECTIVE: The purpose of this study was to focus on short periods of cooling to determine the minimal amount of cooling that may terminate nerve function related to cryo ablation. METHODS: Left and/or right phrenic nerves were dissected from the pericardium and connective tissue of swine (n = 35 preparations). Nerves were placed in a recording chamber modified with a thermocouple array. This apparatus was placed in a digital water bath to maintain an internal chamber temperature of 37°C. Nerves were stimulated proximally with a 1-V, 0.1-ms square wave. Bipolar compound action potentials were recorded proximal and distal to the site of ablation both before and after ablation, then analyzed to determine changes in latency, amplitude, and duration. Temperatures were recorded at a rate of 5 Hz, and maximum cooling rates were calculated. RESULTS: Phrenic nerves were found to elicit compound action potentials upon stimulation for periods up to 4 hours minimum. Average conduction velocity was 56.7 ± 14.7 m/s preablation and 49.8 ± 16.6 m/s postablation (P = .17). Cooling to mild subzero temperatures ceased production of action potentials for >1 hour. CONCLUSION: Taking into account the data presented here, previous publications, and a conservative stance, during cryotherapy applications, cooling of the nerve to below 4°C should be avoided whenever possible.

The benefits of the Atlas of Human Cardiac Anatomy website for the design of cardiac devices.

This paper describes how the Atlas of Human Cardiac Anatomy website can be used to improve cardiac device design throughout the process of development. The Atlas is a free-access website featuring novel images of both functional and fixed human cardiac anatomy from over 250 human heart specimens. This website provides numerous educational tutorials on anatomy, physiology and various imaging modalities. For instance, the 'device tutorial' provides examples of devices that were either present at the time of in vitro reanimation or were subsequently delivered, including leads, catheters, valves, annuloplasty rings and stents. Another section of the website displays 3D models of the vasculature, blood volumes and/or tissue volumes reconstructed from computed tomography and magnetic resonance images of various heart specimens. The website shares library images, video clips and computed tomography and MRI DICOM files in honor of the generous gifts received from donors and their families.

Cardiac remodeling as a consequence of atrial fibrillation: An anatomical study of perfusion-fixed human heart specimens.

BACKGROUND: Atrial fibrillation (AF) causes a continuum of atrial anatomical remodeling. METHODS: Using a library of perfusion-fixed human hearts, specimens with AF were compared to controls. During this preliminary assessment study, direct measurements were taken of atrial volume, pulmonary vein (PV) circumference, and left atrial (LA) wall thicknesses. RESULTS: Hearts with AF typically had larger atrial volumes, as well as a much larger variation in volume compared to controls (range of 59.6-227.1 mL in AF hearts compared to 65.1-115.9 mL in controls). For all hearts, right PVs were larger than left PVs (mean: 171.4 ± 84.6 mm([2]) for right and 118.2 ± 50.1 mm([2]) for left, P < 0.005). LA wall thicknesses ranged from 0.7 mm to 3.1 mm for both AF and control hearts. CONCLUSIONS: Hearts with AF had a large range of sizes which is consistent with the progression of atrial remodeling during AF. The large range of thicknesses will influence the amount of energy needed to create transmural lesions during ablation procedures.

Human glioma cell sensitivity to the sequence-specific alkylating agent methyl-lexitropsin.

PURPOSE: Defining the cytotoxicity of individual adducts in DNA is necessary for mechanistic understanding of human brain tumor resistance to therapeutic alkylating agents and for design of DNA repair-related antiresistance strategies. Our purpose is to characterize the sensitivity of human glioma cells to methyl-lexitropsin (Me-lex), a sequence-specific alkylator that produces 3-methyladenine (3-meA) as the predominant (>90%) DNA lesion. EXPERIMENTAL DESIGN: We quantitated the Me-lex cytotoxicity of 10 human glioma cell lines that differ in O(6)-methylguanine (O(6)-meG)-DNA methyltransferase (MGMT) and mismatch repair activity. We used antisense suppression of alkyladenine DNA glycosylase (AAG) and Ape1 to assess the contribution of 3-meA and abasic sites to lethality and measured abasic sites. RESULTS: (a) The LD(10) for Me-lex varied widely among the cell lines. (b) MGMT-proficient lines were more resistant than MGMT-deficient lines, an unexpected finding because Me-lex produces very little O(6)-meG. (c) Suppression of AAG increased Me-lex killing and reduced abasic site content. (d) Suppression of Ape1 increased Me-lex killing and increased abasic site content. (e) Ablation of MGMT had no effect on Me-lex cytotoxicity. CONCLUSIONS: (a) Me-lex is cytotoxic in human glioma cells and AAG promotes resistance, indicating that 3-meA is a lethal lesion in these cells. (b) Abasic sites resulting from 3-meA repair are cytotoxic and Ape1 promotes resistance to these derivative lesions. (c) A factor(s) associated with MGMT expression, other than repair of O(6)-meG, contributes to Me-lex resistance. (d) Me-lex may have clinical utility in the adjuvant therapy of gliomas. (e) AAG and Ape1 inhibitors may be useful in targeting alkylating agent resistance.

O6-methylguanine-DNA methyltransferase, O6-benzylguanine, and resistance to clinical alkylators in pediatric primary brain tumor cell lines.

PURPOSE: Primary brain tumors are the leading cause of cancer death in children. Our purpose is (a) to assess the contribution of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) to the resistance of pediatric brain tumor cell lines to clinical alkylating agents and (b) to evaluate variables for maximal potentiation of cell killing by the MGMT inhibitor O6-benzylguanine, currently in clinical trials. Few such data for pediatric glioma lines, particularly those from low-grade tumors, are currently available. EXPERIMENTAL DESIGN: We used clonogenic assays of proliferative survival to quantitate cytoxicity of the chloroethylating agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and the methylating agent temozolomide in 11 glioma and five medulloblastoma lines. Twelve lines are newly established and characterized here, nine of them from low-grade gliomas including pilocytic astrocytomas. RESULTS: (a) MGMT is a major determinant of BCNU resistance and the predominant determinant of temozolomide resistance in both our glioma and medulloblastoma lines. On average, O(6)-benzylguanine reduced LD10 for BCNU and temozolomide, 2.6- and 26-fold, respectively, in 15 MGMT-expressing lines. (b) O6-Benzylguanine reduced DT (the threshold dose for killing) for BCNU and temozolomide, 3.3- and 138-fold, respectively. DT was decreased from levels higher than, to levels below, clinically achievable plasma doses for both alkylators. (c) Maximal potentiation by O6-benzylguanine required complete and prolonged suppression of MGMT. CONCLUSIONS: Our results support the use of O6-benzylguanine to achieve full benefit of alkylating agents, particularly temozolomide, in the chemotherapy of pediatric brain tumors.