Jeff R. Anderson

Three-dimensional printing of anatomically accurate, patient specific intracranial aneurysm models.

Objective To develop and validate a method for creating realistic, patient specific replicas of cerebral aneurysms by means of fused deposition modeling. Methods The luminal boundaries of 10 cerebral aneurysms, together with adjacent proximal and distal sections of the parent artery, were segmented based on DSA images, and corresponding virtual three-dimensional (3D) surface reconstructions were created. From these, polylactic acid and MakerBot Flexible Filament replicas of each aneurysm were created by means of fused deposition modeling. The accuracy of the replicas was assessed by quantifying statistical significance in the variations of their inner dimensions relative to 3D DSA images. Feasibility for using these replicas as flow phantoms in combination with phase contrast MRI was demonstrated. Results 3D printed aneurysm models were created for all 10 subjects. Good agreement was seen between the models and the source anatomy. Aneurysm diameter measurements of the printed models and source images correlated well (r=0.999; p<0.001), with no statistically significant group difference (p=0.4) or observed bias. The SDs of the measurements were 0.5 mm and 0.2 mm for source images and 3D models, respectively. 3D printed models could be imaged with flow via MRI. Conclusions The 3D printed aneurysm models presented were accurate and were able to be produced inhouse. These models can be used for previously cited applications, but their anatomical accuracy also enables their use as MRI flow phantoms for comparison with ongoing studies of computational fluid dynamics. Proof of principle imaging experiments confirm MRI flow phantom utility.

A naturally occurring single amino acid replacement in multiple gene regulator of group a streptococcus significantly increases virulence

Single-nucleotide polymorphisms (SNPs) are the most common source of genetic variation within a species; however, few investigations demonstrate how naturally occurring SNPs may increase strain virulence. We recently used group A Streptococcus as a model pathogen to study bacteria strain genotype-patient disease phenotype relationships. Whole-genome sequencing of approximately 800 serotype M59 group A Streptococcus strains, recovered during an outbreak of severe invasive infections across North America, identified a disproportionate number of SNPs in the gene encoding multiple gene regulator of group A Streptococcus (mga). Herein, we report results of studies designed to test the hypothesis that the most commonly occurring SNP, encoding a replacement of arginine for histidine at codon 201 of Mga (H201R), significantly increases virulence. Whole transcriptome analysis revealed that the H201R replacement significantly increased expression of mga and 54 other genes, including many proven virulence factors. Compared to the wild-type strain, a H201R isogenic mutant strain caused significantly larger skin lesions in mice. Serial quantitative bacterial culture and noninvasive magnetic resonance imaging also demonstrated that the isogenic H201R strain was significantly more virulent in a nonhuman primate model of joint infection. These findings show that the H201R replacement in Mga increases the virulence of M59 group A Streptococcus and provide new insight to how a naturally occurring SNP in bacteria contributes to human disease phenotypes.

Validation of computational fluid dynamics methods with anatomically exact, 3D printed MRI phantoms and 4D pcMRI

A new concept of rapid 3D prototyping was implemented using cost-effective 3D printing for creating anatomically correct replica of cerebral aneurysms. With a dedicated flow loop set-up in a full body human MRI scanner, flow measurements were performed using 4D phase contrast magnetic resonance imaging to visualize and quantify intra-aneurysmal flow patterns. Ultrashort TE sequences were employed to obtain high-resolution 3D image data to visualize the lumen inside the plastic replica. In-vitro results were compared with retrospectively obtained in-vivo data and results from computational fluid dynamics simulations (CFD). Rapid prototyping of anatomically realistic 3D models may have future impact in treatment planning, design of image acquisition methods for MRI and angiographic systems and for the design and testing of advanced image post-processing technologies.

Four-Dimensional Phase Contrast Magnetic Resonance Imaging Protocol Optimization Using Patient-Specific 3-Dimensional Printed Replicas for In Vivo Imaging Before and After Flow Diverter Placement

OBJECTIVE Hemodynamics in cerebral aneurysms are currently investigated toward clinical efficacy using nonstandardized computational simulation techniques. At the same time, flow patterns and velocities are accessible by 4-dimensional phase contrast magnetic resonance imaging (4D pcMRI). Complexity of protocol design and imaging duration has limited the use of this technique in clinical imaging. A new approach is presented to overcome these limitations. METHODS Three-dimensional (3D) replicas of 2 cerebral aneurysms were fabricated by fused deposition prototyping (3D printing) and imaged using 4D pcMRI while connected to a magnetic resonance imaging-compatible continuous flow loop. Acquisition parameters were optimized with imaging times not to exceed 10 minutes. Six patients harboring cerebral aneurysms with sizes ranging from 4.7 to 13.8 mm were imaged with the optimized 4D pcMRI protocol. After treatment with the pipeline embolization device (PED), 4D pcMRI examinations were repeated in 3 patients. RESULTS In all cases, major flow patterns were visualized well; smaller aneurysms posed a challenge because of limited spatial resolution, whereas larger aneurysms contained regions of low velocity resulting in limited contrast in the flow-sensitive images. After PED placement, ordered aneurysmal flow was disrupted and intra-aneurysmal velocity was reduced on average by 24.5% (range, 12.9-31.5%). Exploratory statistical analysis yielded a positive significant correlation (P < 0.01) between changes in inflow velocity and posttreatment intra-aneurysmal flow velocity. CONCLUSIONS 4D pcMRI flow imaging in cerebral aneurysms within a time frame suitable for clinical imaging applications is feasible with optimized acquisition parameters, thereby enabling quantification of intra-aneurysmal flow changes after flow diverter device treatment.

Quantification of velocity reduction after flow diverter placement in intracranial aneurysm: An ex vivo study with 3D printed replicas

Phase contrast MRI (pcMRI) was used to measure flow before and after placement of a flow diverter (n = 3). Decreases from 18% to 31% in flow velocity were seen in the inflow jet of the aneurysms. Flow patterns were also compared. It was observed that the gross aneurysmal flow patterns were maintained after flow diverter placement despite decreased fluid velocities. All measurements were carried out in 3D printed aneurysm replicas.

Functional validation of an implantable medical dosing device by MRI at 3T

Sustained release of a small molecule from a prototype implantable drug delivery device was monitored via MRI in an ex vivo tissue phantom over a period of two days. T1 mapping was used as a method to quantify analyte concentration. Continuous, controlled release was observed. The MRI methodology was thus found to be appropriate for device validation and quality assurance/control.

A Semi-automated image segmentation approach for computational fluid dynamics studies of aortic dissection

Computational studies of aortic hemodynamics require accurate and reproducible segmentation of the aortic tree from whole body, contrast enhanced CT images. Three methods were vetted for segmentation. A semi-automated approach that utilizes denoising, the extended maxima transform, and a minimal amount of manual segmentation was adopted.