Toward a noninvasive estimate of interstitial fluid pressure by dynamic contrast‐enhanced <scp>MRI</scp> in a rat model of cerebral tumor

Elmghirbi, Rasha; Nagaraja, Tavarekere N.; Brown, Stephen L.; Keenan, Kelly A.; Panda, Swayamprava; Cabral, Glauber; Bagher‐Ebadian, Hassan; Divine, George; Lee, Ian Y.; Ewing, James R.

doi:10.1002/mrm.27163

Cited by 23 publications

(27 citation statements)

References 34 publications

(87 reference statements)

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“…Another approach used by several works is dynamic contrast enhanced MRI where fluid flow velocity at the tumour surface is estimated by examining contrast agent over time [12][13][14] . This velocity can then be used to estimate IFP by assuming or estimating hydraulic conductivity and related parameters 15,16 . Alternatively, this velocity can be used as a stand-in for IFP as strong correlation has been shown in some cases 17 and recent work showed it may be a prognostic factor in cervical cancer 18 .…”

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confidence: 99%

Towards noninvasive estimation of tumour pressure by utilising MR elastography and nonlinear biomechanical models: a simulation and phantom study

Fovargue

Fiorito

Capilnasiu

et al. 2020

Sci Rep

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The solid and fluid pressures of tumours are often elevated relative to surrounding tissue. This increased pressure is known to correlate with decreased treatment efficacy and potentially with tumour aggressiveness and therefore, accurate noninvasive estimates of tumour pressure would be of great value. We present a proof-of-concept method to infer the total tumour pressure, that is the sum of the fluid and solid parts, by examining stiffness in the peritumoural tissue with MR elastography and utilising nonlinear biomechanical models. The pressure from the tumour deforms the surrounding tissue leading to changes in stiffness. Understanding and accounting for these biases in stiffness has the potential to enable estimation of total tumour pressure. Simulations are used to validate the method with varying pressure levels, tumour shape, tumour size, and noise levels. Results show excellent matching in low noise cases and still correlate well with higher noise. Percent error remains near or below 10% for higher pressures in all noise level cases. Reconstructed pressures were also calculated from experiments with a catheter balloon embedded in a plastisol phantom at multiple inflation levels. Here the reconstructed pressures generally match the increases in pressure measured during the experiments. Percent errors between average reconstructed and measured pressures at four inflation states are 17.9%, 52%, 23.2%, and 0.9%. Future work will apply this method to in vivo data, potentially providing an important biomarker for cancer diagnosis and treatment.

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confidence: 99%

Towards noninvasive estimation of tumour pressure by utilising MR elastography and nonlinear biomechanical models: a simulation and phantom study

Fovargue

Fiorito

Capilnasiu

et al. 2020

Sci Rep

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“…Accurate measurement of interstitial hypertension in human tumors with IFP probes is technically challenging, time consuming, and can only be performed for superficial tumors. Significant efforts are currently being made to develop MRI-based assays for assessment of tumor IFP, and promising assays have been reported [8], [41], [42]. However, these assays are in an early stage of development, and strategies for improving the assays are currently under investigation.…”

Section: Discussionmentioning

confidence: 99%

Intratumor Heterogeneity in Interstitial Fluid Pressure in Cervical and Pancreatic Carcinoma Xenografts

Hansem¹,

Huang²,

Wegner³

et al. 2019

Translational Oncology

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Preclinical studies have suggested that interstitial fluid pressure (IFP) is uniformly elevated in the central region of tumors, whereas clinical studies have revealed that IFP may vary among different measurement sites in the tumor center. IFP measurements are technically difficult, and it has been claimed that the intratumor heterogeneity in IFP reported for human tumors is due to technical problems. The main purpose of this study was to determine conclusively whether IFP may be heterogeneously elevated in the central tumor region, and if so, to reveal possible mechanisms and possible consequences. Tumors of two xenograft models were included in the study: HL-16 cervical carcinoma and Panc-1 pancreatic carcinoma. IFP was measured with Millar SPC 320 catheters in two positions in each tumor and related to tumor histology or the metastatic status of the host mouse. Some tumors of both models showed significant intratumor heterogeneity in IFP, and this heterogeneity was associated with a compartmentalized histological appearance (i.e., the tissue was divided into compartments separated by thick connective tissue bands) in HL-16 tumors and with a dense collagen-I-rich extracellular matrix in Panc-1 tumors, suggesting that these connective tissue structures prevented efficient interstitial convection. Furthermore, some tumors of both models developed lymph node metastases, and of the two IFP values measured in each tumor, only the higher value was significantly higher in metastatic than in non-metastatic tumors, suggesting that metastatic propensity was determined by the tumor region having the highest IFP.

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“…Thirty-two female, athymic, immune-compromised rats were randomly distributed between the 3 subgroups, M0, M− and M +. Following published methods [ 31 , 32 ], one of the two neurosphere cell lines was implanted into the right hemisphere in these rats under a protocol approved by the Institutional Animal Care and Use Committee. Briefly, animals were anesthetized with isoflurane (4% for induction, 1.5% for maintenance, balance N 2 O:O 2 = 2:1).…”

Section: Methodsmentioning

confidence: 99%

The impact of initial tumor microenvironment on imaging phenotype

Nagaraja

deCarvalho

Brown

et al. 2021

Cancer Treatment and Research Communications

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Models of human cancer, to be useful, must replicate human disease with high fidelity. Our focus in this study is rat xenograft brain tumors as a model of human embedded cerebral tumors. A distinguishing signature of such tumors in humans, that of contrast-enhancement on imaging, is often not present when the human cells grow in rodents, despite the xenografts having nearly identical DNA signatures to the original tumor specimen. Although contrast enhancement was uniformly evident in all the human tumors from which the xenografts’ cells were derived, we show that long-term contrast enhancement in the model tumors may be determined conditionally by the tumor microenvironment at the time of cell implantation. We demonstrate this phenomenon in one of two patient-derived orthotopic xenograft (PDOX) models using cancer stem-like cell (CSC)-enriched neurospheres from human tumor resection specimens, transplanted to groups of immune-compromised rats in the presence or absence of a collagen/fibrin scaffolding matrix, Matrigel. The rats were imaged by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and their brains were examined by histopathology. Targeted proteomics of the PDOX tumor specimens grown from CSC implanted with and without Matrigel showed that while the levels of the majority of proteins and post-translational modifications were comparable between contrast-enhancing and non-enhancing tumors, phosphorylation of Fox038 showed a differential expression. The results suggest key proteins determine contrast enhancement and suggest a path toward the development of better animal models of human glioma. Future work is needed to elucidate fully the molecular determinants of contrast-enhancement.

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Toward a noninvasive estimate of interstitial fluid pressure by dynamic contrast‐enhanced MRI in a rat model of cerebral tumor

Abstract: This research suggests that MRI dynamic studies contain enough information to noninvasively estimate TIFP in this, and possibly other, tumor models, and thus might be used to assess tumor aggressiveness and response to therapy.

Cited by 23 publications

References 34 publications

Towards noninvasive estimation of tumour pressure by utilising MR elastography and nonlinear biomechanical models: a simulation and phantom study

Towards noninvasive estimation of tumour pressure by utilising MR elastography and nonlinear biomechanical models: a simulation and phantom study

Intratumor Heterogeneity in Interstitial Fluid Pressure in Cervical and Pancreatic Carcinoma Xenografts

The impact of initial tumor microenvironment on imaging phenotype

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