Name: image-guided convection-enhanced delivery into agarose gel models of the brain
Uploaded: 2014-05-14T13:45:00
Description: Watch this Scientific Journal Video about Image-guided Convection-enhanced Delivery into Agarose Gel Models of the Brain at JoVE.com

The authors would like to thank the staff from the MRI facilities at the Semmes-Murphey Clinic, Memphis, Tennessee as well as the Neurosurgical department at The University of Tennessee Health Science Center in Memphis, Tennessee.

1. Preparation of Gel Phantoms and Dye
<ol>
	<li>Prepare 0.2% agarose gel by dissolving 2 g of 0.1% agarose powder in 1,000 ml of deionized water. Stir the solution for approximately 1 min to insure proper mixing; and immediately microwave the solution in 3 min intervals for 9 min or until clear, stirring between intervals.</li>
	<li>While the agarose gel is liquid, pour the solution into 5 cm x 5 cm x 5 cm containers. Allow space at the top of the container to add water and allow the agarose gel to cool and settle.</l...

<ol>
	<li>Miranpuri, G. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gene-based+therapy+of+Parkinson's+Disease:+Translation+from+animal+model+to+human+clinical+trial+employing+convection+enhanced+delivery.">Gene-based therapy of Parkinson's Disease: Translation from animal model to human clinical trial employing convection enhanced delivery.</a> Annals of Neurosciences. 19, 133-146 (2012).</li><li>Sillay, K., Hinchman, A., Akture, E., Salamat, S., Miranpuri, G., Williams, J., Berndt, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Convection+Enhanced+Delivery+to+the+Brain:+Preparing+for+Gene+Therapy+and+Protein+Delivery+to+the+Brain+for+Functional+and+Restorative+Neurosurgery+by+Understanding+Low-Flow+Neurocatheter+Infusions+Using+the+Alaris&#174;+System+Infusion+Pump.">Convection Enhanced Delivery to the Brain: Preparing for Gene Therapy and Protein Delivery to the Brain for Functional and Restorative Neurosurgery by Understanding Low-Flow Neurocatheter Infusions Using the Alaris&#174; System Infusion Pump.</a> Annals of Neurosciences. 20, (2013).</li><li>Song, D. K., Lonser, R. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Convection-enhanced+delivery+for+the+treatment+of+pediatric+neurologic+disorders.">Convection-enhanced delivery for the treatment of pediatric neurologic disorders.</a> Journal of child neurology. 23, 1231-1237 (2008).</li><li>Bobo, R. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Convection-enhanced+delivery+of+macromolecules+in+the+brain.">Convection-enhanced delivery of macromolecules in the brain.</a> Proc Natl Acad Sci USA. 91, 2076-2080 (1994).</li><li>Debinski, W., Tatter, S. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Convection-enhanced+delivery+for+the+treatment+of+brain+tumors.">Convection-enhanced delivery for the treatment of brain tumors.</a> Expert review of neurotherapeutics. 9, 1519-1527 (2009).</li><li>Morrison, P. F., Laske, D. W., Bobo, H., Oldfield, E. H., Dedrick, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High-flow+microinfusion:+tissue+penetration+and+pharmacodynamics.">High-flow microinfusion: tissue penetration and pharmacodynamics.</a> The American journal of physiology. 266, 292-305 (1994).</li><li>Nguyen, T. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Convective+distribution+of+macromolecules+in+the+primate+brain+demonstrated+using+computerized+tomography+and+magnetic+resonance+imaging.">Convective distribution of macromolecules in the primate brain demonstrated using computerized tomography and magnetic resonance imaging.</a> Journal of neurosurgery. 98, 584-590 (2003).</li><li>Lonser, R. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Successful+and+safe+perfusion+of+the+primate+brainstem:+in+vivo+magnetic+resonance+imaging+of+macromolecular+distribution+during+infusion.">Successful and safe perfusion of the primate brainstem: in vivo magnetic resonance imaging of macromolecular distribution during infusion.</a> Journal of neurosurgery. 97, 905-913 (2002).</li><li>Raghavan, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Convection-enhanced+delivery+of+therapeutics+for+brain+disease,+and+its+optimization.">Convection-enhanced delivery of therapeutics for brain disease, and its optimization.</a> Neurosurg Focus. 20, (2006).</li><li>Sillay, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Benchmarking+the+ERG+valve+tip+and+MRI+Interventions+Smart+Flow+neurocatheter+convection-enhanced+delivery+system's+performance+in+a+gel+model+of+the+brain:+employing+infusion+protocols+proposed+for+gene+therapy+for+Parkinson's+disease.">Benchmarking the ERG valve tip and MRI Interventions Smart Flow neurocatheter convection-enhanced delivery system's performance in a gel model of the brain: employing infusion protocols proposed for gene therapy for Parkinson's disease.</a> Journal of neural engineering. 9, (2012).</li><li>Schomberg, D., Wang, A., Marshall, H., Sillay, K., Miranpuri, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ramped-Rate+vs.+continuous+rate+infusions:+An+in+vitro+comparison+of+Convection+Enhanced+Delivery+protocols.">Ramped-Rate vs. continuous rate infusions: An in vitro comparison of Convection Enhanced Delivery protocols.</a> Annals of Neurosciences. 20, (2013).</li><li>Sillay, K. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Perioperative+Brain+Shift+and+Deep+Brain+Stimulating+Electrode+Deformation+Analysis:+Implications+for+rigid+and+non-rigid+devices.">Perioperative Brain Shift and Deep Brain Stimulating Electrode Deformation Analysis: Implications for rigid and non-rigid devices.</a> Ann Biomed Eng. 41, 293-304 (2013).</li><li>Brodsky, E., Block, W., Alexander, A., Emborg, M., Ross, C., Sillay, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intraoperative+Device+Targeting+using+Real-Time+MRI.">Intraoperative Device Targeting using Real-Time MRI.</a> Biomedical Sciences and Engineering Conference, BSEC. , (2011).</li><li>Sillay, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Strategies+for+the+delivery+of+multiple+collinear+infusion+clouds+in+convection-enhanced+delivery+in+the+treatment+of+Parkinson's+disease.">Strategies for the delivery of multiple collinear infusion clouds in convection-enhanced delivery in the treatment of Parkinson's disease.</a> Stereotactic and functional neurosurgery. 91, 153-161 (2013).</li><li>Brady, M. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathways+of+infusate+loss+during+convection-enhanced+delivery+into+the+putamen+nucleus.">Pathways of infusate loss during convection-enhanced delivery into the putamen nucleus.</a> Stereotactic and functional neurosurgery. 91, 69-78 (2013).</li><li>White, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+evaluation+of+the+relationships+between+catheter+design+and+tissue+mechanics+in+achieving+high-flow+convection-enhanced+delivery.">An evaluation of the relationships between catheter design and tissue mechanics in achieving high-flow convection-enhanced delivery.</a> J Neurosci Methods. 199, 87-97 (2011).</li><li>Fiandaca, M. S., Forsayeth, J. R., Dickinson, P. J., Bankiewicz, K. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Image-guided+convection-enhanced+delivery+platform+in+the+treatment+of+neurological+diseases.">Image-guided convection-enhanced delivery platform in the treatment of neurological diseases.</a> Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 5, 123-127 (2008).</li><li>Jagannathan, J., Walbridge, S., Butman, J. A., Oldfield, E. H., Lonser, R. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+ependymal+and+pial+surfaces+on+convection-enhanced+delivery.">Effect of ependymal and pial surfaces on convection-enhanced delivery.</a> Journal of neurosurgery. 109, 547-552 (2008).</li><li>Chen, Z. J., Broaddus, W. C., Viswanathan, R. R., Raghavan, R., Gillies, G. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intraparenchymal+drug+delivery+via+positive-pressure+infusion:+experimental+and+modeling+studies+of+poroelasticity+in+brain+phantom+gels.">Intraparenchymal drug delivery via positive-pressure infusion: experimental and modeling studies of poroelasticity in brain phantom gels.</a> IEEE transactions on bio-medical engineering. 49, 85-96 (2002).</li><li>Chen, Z. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+realistic+brain+tissue+phantom+for+intraparenchymal+infusion+studies.">A realistic brain tissue phantom for intraparenchymal infusion studies.</a> Journal of neurosurgery. 101, 314-322 (2004).</li><li>Richardson, R. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interventional+MRI-guided+Putaminal+Delivery+of+AAV2-GDNF+for+a+Planned+Clinical+Trial+in+Parkinson's+Disease.">Interventional MRI-guided Putaminal Delivery of AAV2-GDNF for a Planned Clinical Trial in Parkinson's Disease.</a> Mol Ther. 19, 1048-1057 (2011).</li><li>Thorne, R. G., Hrabetova, S., Nicholson, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diffusion+of+epidermal+growth+factor+in+rat+brain+extracellular+space+measured+by+integrative+optical+imaging.">Diffusion of epidermal growth factor in rat brain extracellular space measured by integrative optical imaging.</a> Journal of neurophysiology. 92, 3471-3481 (2004).</li><li>Panse, S. J., Fillmore, H. L., Chen, Z. J., Gillies, G. T., Broaddus, W. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+coaxial+tube+catheter+for+central+nervous+system+infusions:+performance+characteristics+in+brain+phantom+gel.">A novel coaxial tube catheter for central nervous system infusions: performance characteristics in brain phantom gel.</a> J Med Eng Technol. 35, 408-414 (2010).</li><li>Linninger, A. A., Somayaji, M. R., Zhang, L., Smitha Hariharan, M., Penn, R. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rigorous+mathematical+modeling+techniques+for+optimal+delivery+of+macromolecules+to+the+brain.">Rigorous mathematical modeling techniques for optimal delivery of macromolecules to the brain.</a> IEEE transactions on bio-medical engineering. 55, 2303-2313 (2008).</li><li>Sampson, J. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+utility+of+a+patient-specific+algorithm+for+simulating+intracerebral+drug+infusions.">Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions.</a> Neuro-oncology. 9, 343-353 (2007).</li></ol>

The critical steps for ensuring the success of the infusion are: purging the infusion line of air, mixing the agarose gel, analyzing the MR data, using small inner catheter diameters, using stepped catheter designs to minimize backflow, and minimizing the pressure felt by the gel or tissue into which the drug is being infused. As previously stated, the main detriment to the success of the infusion is infusion line air. Correctly and thoroughly purging the infusion line of air is critical to ensure no air enters the infus...

Convection-enhanced delivery (CED) has been proposed as a treatment option for a broad spectrum of neurological disorders including malignant brain tumors, epilepsy, metabolic disorders, neurodegenerative diseases (such as Parkinson disease)1, stroke, and trauma2. CED employs positive pressure bulk flow for the distribution of a drug or other infusate. CED provides safe, reliable, and homogenous delivery of molecular weight compounds, ranging from low to high, at clinically relevant volumes3. Traditional drug delivery to brain tissue is severely restricted by the blood-brain barrier4. Formed by the tight junctions between endothelial cells that make up the capillaries in the brain, the blood-brain barrier blocks polar and high molecular weight molecules from entering the parenchyma of the brain. Direct intraparenchymal brain infusion via CED can overcome the limitations of previous therapeutic drug delivery modalities and allows the use of therapeutic agents that would not cross the blood-brain barrier, and therefore have been previously unavailable as viable treatment options5.
Researchers from the US National Institutes of Health (NIH) described CED in the early 1990s as a means of achieving greater therapeutic drug concentrations than by diffusion alone6-8. The first methods of CED involved implanting one or more catheters into the brain, connecting an infusion pump to the catheter, and pumping the therapeutic agents directly into the targeted region. The increased distribution fraction and relatively stable concentration is reported to occur as the positive pressure created by the infusion pump causes the tissues to dilate and allow for permeation of the drug9.
The fundamental technique for CED remains largely the same as it was first described. Advances in catheter design10, infusion technique11, line pressure monitoring2, and real time MRI monitoring to correct for brain shift12,13, optimize multiple collinear infusions14, and monitor for infusate loss15 have increased the safety and efficacy of the treatment10. Additional importance has been placed on the catheter design and infusion strategy including flow rate. Successful CED, with limited catheter reflux and tissue damage, has been correlated with catheter design and infusion rate. The use of a catheter with a narrow diameter and a low infusion rate to limit backflow along the brain-catheter interface as well as limit damage at the catheter tip16. MR imaging provides visual confirmation of the correct location for infusion catheter placement, and thus drug delivery, while also allowing for correction of infusion reflux or aberrant delivery17. MR images can also be used to approximate and track the volumes of distribution (Vd) of the infused drug. The Vd is calculated using an MR imaging signal intensity value greater than three standard deviations above the mean from the surrounding non-infused gel as a threshold for segmentation18. The Vd is a useful measurement for CED because it represents the volume of the drug distributed in the brain. Along with the volume infused (Vi), a ratio can be generated (Vd/Vi) quantifying the volume covered by the infused drug.
Agarose gel phantoms mimic several crucial mechanical properties of the human brain important for understanding CED such as: Vd, gel-catheter interactions, poroelastic properties, and infusion cloud morphology10. Mixtures of 0.2% agarose gel have been shown to mimic in vivo changes in local pore fraction caused by gel dilation due to CED. A similar pore fraction to human brain promotes similar interactions and accurate measurements of Vd19. Additionally, similar concentrations of agarose gels such as 0.6% and 0.8% have shown similar infusion pressure profiles to the brain20. Further, the translucent agarose gels provide the advantage of real-time visualization of catheter placement and infusion reflux. Agarose gel phantoms are relatively inexpensive to produce. The cost of the agarose gel phantoms may be key to future widespread training throughout neurological surgery. Due to these properties, agarose gels provide a useful surrogate, replicating many of the key attributes of human brain infusions without the use of brain tissue.
As stated above, image-guided CED into agarose gel models provides a beneficial in vitro method for testing, research, and training.&#160; The purpose of this article is to describe how to recreate agarose gel phantoms, to outline appropriate CED testing and analysis protocols, and to address common errors faced during CED infusions for the treatment of neurological disease.

<table border="0" cellpadding="0" cellspacing="0" width="590">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:205px;">Prohance</td>
			<td style="width:71px;">Bracco</td>
			<td style="width:119px;"></td>
			<td style="width:195px;">Gadoteridol radio contrast media</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:205px;">Bromophenol Blue Dye</td>
			<td style="width:71px;">Biorad</td>
			<td style="width:119px;">161-0404</td>
			<td>Dye for infusate visualization</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:205px;">Agarose Gel Powder</td>
			<td style="width:71px;">Biorad</td>
			<td style="width:119px;">161-3101EDU</td>
			<td>Agarose powder for creating gels</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:205px;">Medrad Veris MR Vital Signs Monitor</td>
			<td style="width:71px;">Medrad</td>
			<td style="width:119px;"></td>
			<td>MR safe infusion pressure monitor</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:205px;">16 Gauge SmartFlow Catheter</td>
			<td style="width:71px;">SurgiVision</td>
			<td style="width:119px;"></td>
			<td>Infusion catheter</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:205px;">Medrad Continuum MR Infusion System</td>
			<td style="width:71px;">Medrad</td>
			<td style="width:119px;"></td>
			<td>MR safe infusion pump</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:205px;">SMART Frame MRI Guided Trajectory Frame</td>
			<td style="width:71px;">ClearPoint</td>
			<td style="width:119px;"></td>
			<td>Infusion catheter frame</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:205px;">Osirix Imaging Software and DICOM Viewer</td>
			<td style="width:71px;">Osirix Imaging Software</td>
			<td style="width:119px;"></td>
			<td>OsiriX 32-bit DICOM Viewer</td>
		</tr>
	</tbody>
</table>

image-guided convection-enhanced delivery into agarose gel models of the brain

Convection-enhanced delivery (CED) has been proposed as a treatment option for a wide range of neurological diseases. Neuroinfusion catheter CED allows for positive pressure bulk flow to deliver greater quantities of therapeutics to an intracranial target than traditional drug delivery methods. The clinical utility of real time MRI guided CED (rCED) lies in the ability to accurately target, monitor therapy, and identify complications. With training, rCED is efficient and complications may be minimized. The agarose gel model of the brain provides an accessible tool for CED testing, research, and training. Simulated brain rCED allows practice of the mock surgery while also providing visual feedback of the infusion. Analysis of infusion allows for calculation of the distribution fraction (Vd/Vi) allowing the trainee to verify the similarity of the model as compared to human brain tissue. This article describes our agarose gel brain phantom and outlines important metrics during a CED infusion and analysis protocols while addressing common pitfalls faced during CED infusion for the treatment of neurological disease.

Interpreting and analyzing CED infusions involve several important factors such as distribution fraction and infusate reflux. The distribution fraction calculation depends heavily upon the calculation of the Vd. Therefore accurate interpretation of the MR images is critical. We propose a semi-automated method for reliably reproducing these measurements as listed above. These methods objectively determine the cross sectional area of the infusate cloud and an approximate radius. While variable, in agarose gel the infusion ...

Watch this Scientific Journal Video about Image-guided Convection-enhanced Delivery into Agarose Gel Models of the Brain at JoVE.com

Image-guided Convection-enhanced Delivery into Agarose Gel Models of the Brain

Convection-enhanced delivery (CED) has been proposed as a treatment option for a wide range of neurological diseases. In order to prepare health care professionals for adoption of CED, accessible training models are needed. We describe the use of agarose gel as such a model of the human brain for testing, research, and training.

Convection-enhanced delivery (CED) has been proposed as a treatment option for a wide range of neurological diseases. Neuroinfusion catheter CED allows ...

Research

JoVE Journal

Medicine

MRI and PET in Mouse Models of Myocardial Infarction

Myocardial infarction is one of the leading causes of death in the Western world. The similarity of the mouse heart to the human heart has made it an ...

DNBS/TNBS Colitis Models: Providing Insights Into Inflammatory Bowel Disease and Effects of Dietary Fat

Inflammatory Bowel Diseases (IBD), including Crohn&#39;s Disease and Ulcerative Colitis, have long been associated with a genetic basis, and more recently ...

Heterotopic Mucosal Engrafting Procedure for Direct Drug Delivery to the Brain in Mice

Delivery of therapeutics into the brain is impeded by the presence of the blood-brain barrier (BBB) which restricts the passage of polar and high ...

Mouse Kidney Transplantation: Models of Allograft Rejection

Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. The mouse model of renal transplantation closely ...

Transposon Mediated Integration of Plasmid DNA into the Subventricular Zone of Neonatal Mice to Generate Novel Models of Glioblastoma

An urgent need exists to test the contribution of new genes to the pathogenesis and progression of human glioblastomas (GBM), the most common primary ...

Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells

Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells

The aim of this protocol presents an optimized procedure for the purification and cultivation of pBECs and to establish in vitro blood-brain barrier (BBB) ...

Image-Guided Resection of Glioblastoma and Intracranial Implantation of Therapeutic Stem Cell-seeded Scaffolds

Glioblastoma (GBM), the most common and aggressive primary brain cancer, carries a life expectancy of 12-15 months. The short life expectancy is due in ...

Predicting Treatment Response to Image-Guided Therapies Using Machine Learning: An Example for Trans-Arterial Treatment of Hepatocellular Carcinoma

Intra-arterial therapies are the standard of care for patients with hepatocellular carcinoma who cannot undergo surgical resection. The objective of this ...

An Image Guided Transapical Mitral Valve Leaflet Puncture Model of Controlled Volume Overload from Mitral Regurgitation in the Rat

Mitral regurgitation (MR) is a widely prevalent heart valve lesion, which causes cardiac remodeling and leads to congestive heart failure. Though the ...

Intratracheal Administration of Dry Powder Formulation in Mice

In the development of inhalable dry powder formulations, it is essential to evaluate their biological activities in preclinical animal models. This paper ...