Uterine perfusion model for analyzing barriers to transport in fibroids

Stirland, Darren L.; Nichols, Joseph W.; Jarboe, Elke A.; Adelman, Marisa R.; Dassel, Mark; Janát-Amsbury, Margit M.; Bae, You Han

doi:10.1016/j.jconrel.2015.07.006

Cited by 9 publications

(9 citation statements)

References 33 publications

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“…As reported by other works that have performed ex vivo uterine perfusion, some uterus specimens are more difficult to perfuse due to variations in uterine vasculature and amount of vasculature cauterization after surgical excision. The MR‐compatible extracorpeal perfusion technique used for this study did not use any feedback control systems to monitor the temperature, pressure and pH values in the perfusate and reperfused tissue.…”

Section: Discussionmentioning

confidence: 95%

“…While the data sets obtained from each tissue sample ranged in completeness, this set of measured properties represents a step forward in availability of patient-specific properties. However, even though the ex vivo testing was designed to mimic the in vivo As reported by other works that have performed ex vivo uterine perfusion, 28,51 some uterus specimens are more difficult to perfuse due to variations in uterine vasculature and amount of vasculature cauterization after surgical excision. The MR-compatible extracorpeal perfusion technique used for this study did not use any feedback control systems to monitor the temperature, pressure and pH values in the perfusate and reperfused tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Catheters were sutured to the tissue to mitigate back flow and prevent unintentional removal. Following cannulation, specimens were flushed with a Modified Krebs-Henseleit Buffer, 28,29 an isotonic solution that is fortified with glucose, heparin, and insulin. Once the buffer perfusate passively exiting the uterine veins appeared clear (~30 min), specimens were submerged in a recirculating bath of the perfusate maintained at a constant temperature of 37°C.…”

Section: C Cannulation and Tissue Preparationmentioning

confidence: 99%

“…presents both a schematic and photograph of the MR-compatible experimental setup designed to maintain tissue viability. While other studies have developed systems for reperfusion of the uterus,28,29 this work required modifications to operate in the MR environment.…”

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confidence: 99%

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A tissue preparation to characterize uterine fibroid tissue properties for thermal therapies

et al. 2019

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Purpose Treating uterine fibroids with less invasive therapies such as magnetic resonance‐guided focused ultrasound (MRgFUS) is an attractive alternative to surgery. Treatment planning can improve MRgFUS procedures and reduce treatment times, but the tissue properties that currently inform treatment planning tools are not adequate. This study aims to develop an ex vivo uterine fibroid model that can emulate the in vivo environment allowing for characterization of the uterus and fibroid MR, acoustic, and thermal tissue properties while maintaining viability for the necessary postsurgical histopathological assessments. Methods Women undergoing a hysterectomy due to fibroid‐related symptoms were invited to undergo a preoperative pelvic MRI and to permit postoperative testing of their uterine specimen. Patients that declined or could not be scheduled for a pre‐operative MRI were still able to allow post‐operative testing of their excised tissue. Following surgical removal of the uterus, nonmorcellated tissues were reperfused with a Krebs‐Henseleit buffer solution. An MR‐compatible perfusion system was designed to maintain tissue viability inside the MR suite during scanning. MR imaging protocols utilized preoperatively were repeated on whole sample, reperfused ex vivo uterus specimens. Thermal properties including thermal diffusivity and thermal conductivity of the uterus and fibroids were determined using an invasive needle sensor device in 50% of the specimens. Acoustic property measurements (density, speed of sound and attenuation) were obtained for approximately 20% of the tissue samples using both through‐transmission and radiation force balance techniques. Differences between fibroid and uterus and in vivo and ex vivo measurements were evaluated with a two‐tailed Student t test. Results Fourteen patients participated in the study and measurements were obtained from 22 unique fibroids. Of the 16 fibroids available for preoperative MRI testing, 69% demonstrated classic hypo‐intensity relative to the myometrium, with the remainder presenting with iso‐ (25%) or hyper‐intensity (6%). While thermal diffusivity was not significantly different between fibroid and myometrium tissues (0.217 ± 0.047 and 0.204 ± 0.039 mm2/s, respectively), the acoustic attenuation in fibroid tissue was significantly higher than myometrium (0.092 ± 0.021 and 0.052 ± 0.023 Np/cm/MHz, respectively). When comparing in vivo with ex vivo MRI T1 and T2 measurements in fibroids and myometrium tissue, the only difference was found in the fibroid T2 property (P < 0.05). Finally, the developed perfusion protocol successfully maintained tissue viability in ex vivo tissues as evaluated through histological analysis. Conclusions This study developed an MR‐compatible extracorporeal perfusion technique that effectively maintains tissue viability, allowing for the direct measurement of patient‐specific MR, thermal, and acoustic property values for both fibroid and myometrium tissues. These measured tissue property values will enable further development and...

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: C Cannulation and Tissue Preparationmentioning

confidence: 99%

mentioning

confidence: 99%

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A tissue preparation to characterize uterine fibroid tissue properties for thermal therapies

et al. 2019

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“…Three hours after the final dose, the mice were sacrificed and 1,1’ - Dioctadecyl - 3,3,3’,3’ - tetramethylindodicarbocyanine iodide (DiD) (84903, Anaspec, Fremont, CA) was introduced by cardiac perfusion to fluorescently stain the blood vessels. This vessel staining protocol was previously found to be adequate in staining even the small vessels of densely packed human fibroid tissue [4]. Following perfusion, the liver and tumor tissues were collected and placed in Optimal Cutting Temperature compound for at least 5 minutes before flash freezing with isopentane in a metal beaker cooled by liquid nitrogen.…”

Section: Materials/methodsmentioning

confidence: 99%

Analyzing spatiotemporal distribution of uniquely fluorescent nanoparticles in xenograft tumors

Stirland

Matsumoto

Toh

et al. 2016

Journal of Controlled Release

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A dose circulating through the blood at one time will have different opportunities to access the tumor compared to a dose circulating hours later. Methods to test this hypothesis allowed us to differentiate two uniquely fluorescent doses of nanoparticles (administered as a mixture or sequentially) and to measure the distribution and correlation of these nanoparticle doses in three dimensions. Multiple colocalization analyses confirm that silica nanoparticles separated into different dose administrations will not accumulate in the same location. Decreased colocalization between separate doses implies dynamic extravasation events on the scale of microns. Further, the perfusion state of different blood vessels can change across the dosing period. Lastly, analyzing the distance traveled by these silica nanoparticles in two dimensions can be an overestimation when compared with three-dimensional distance analysis. Better understanding intratumoral distribution of delivered drugs will be crucial to overcoming the various barriers to transport in solid tumors.

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Smart Nanotechnologies to Target Tumor with Deep Penetration Depth for Efficient Cancer Treatment and Imaging

Xue

Dixon

Glen-Ravenhill

et al. 2019

Advanced Therapeutics

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Nanomedicines have long been expected to significantly enhance cancer treatment. However, their clinical translation is still very limited despite of the world's great efforts during the last 2 decades. One of the reasons is that the transport barriers within tumors restrict their penetration into tumors, with most nanomedicines remaining among the top submicrometer to several micrometers scale. Therefore, there is an extensive interest in the field to understand the tumor microenvironment and develop techniques to boost the penetration of nanomedicines in tumors. This review emphasizes the need of smart nanotechnology to fit the changing requirements of nanomedicines for effective drug delivery, particularly the technologies for deep penetration of nanomedicines in tumor tissues, and explores their mechanisms in order to achieve multistage requirement during the applications of nanomedicines in patients. Finally, the advantages and

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Uterine perfusion model for analyzing barriers to transport in fibroids

Cited by 9 publications

References 33 publications

A tissue preparation to characterize uterine fibroid tissue properties for thermal therapies

A tissue preparation to characterize uterine fibroid tissue properties for thermal therapies

Analyzing spatiotemporal distribution of uniquely fluorescent nanoparticles in xenograft tumors

Smart Nanotechnologies to Target Tumor with Deep Penetration Depth for Efficient Cancer Treatment and Imaging

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