Effect of hyperosmotic blood-brain barrier disruption on transcapillary transport in canine brain tumors

1990 ◽  
Vol 72 (3) ◽  
pp. 441-449 ◽  
Author(s):  
Dennis R. Groothuis ◽  
Peter C. Warkne ◽  
Peter Molnar ◽  
Gregory D. Lapin ◽  
Michael A. Mikhael
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Ct Scan ◽  
Compartment Model ◽  
Two Compartment Model ◽  
Before And After ◽  
Meglumine Iothalamate ◽  
The Brain ◽  
Time Point

✓ Whether hyperosmotic blood-brain barrier (BBB) disruption is a technique that can be used to increase permeability of brain-tumor capillaries and thereby transiently increase drug delivery to the brain tumor is controversial. Nine virally induced brain tumors were studied in seven dogs, before and after hyperosmotic BBB disruption with 1.4 osmolar mannitol. Each dog was studied with computerized tomography (CT) after administration of the water-soluble tracer meglumine iothalamate. Each study lasted 30 minutes. A baseline CT scan and 35 to 40 additional CT scans were obtained to provide a time-related measurement of the amount of meglumine iothalamate in tissue (Am(t)), and 30 plasma samples were collected to provide the time-related measurement of meglumine iothalamate in plasma (Cp(t)). The data were analyzed by three different methods: 1) a two-compartment model and nonlinear curve fitting were used to calculate K1 (blood-to-tissue or influx constant), k2 (tissue-to-blood or efflux constant), and Vp (plasma vascular space); 2) K1 values were calculated with a two-compartment model, assuming no efflux, at the time point for each CT scan; and 3) a “tissue advantage ratio” was calculated that expressed the ratio of tissue uptake of meglumine iothalamate at each time point, comparing values before and after BBB disruption. Regardless of which method of data analysis was used, there was a marked and significant increase in transcapillary transport of meglumine iothalamate to tumor-free brain regions, while there was only a small, transient, and insignificant increase to the brain tumors. Although there were often marked increases in delivery to cortex in the same hemisphere as the tumors, there was no significant increase to brain immediately surrounding the tumors, perhaps due to altered circulatory dynamics in this region. These data raise serious questions as to the wisdom of using this technique to increase drug delivery to brain tumors in patients and strongly support the continued study of this technique in experimental brain tumors before it is used in patients.

Enhanced therapeutic agent delivery through magnetic resonance imaging–monitored focused ultrasound blood-brain barrier disruption for brain tumor treatment: an overview of the current preclinical status

2012 ◽  
Vol 32 (1) ◽  
pp. E4 ◽  
Author(s):  
Hao-Li Liu ◽  
Hung-Wei Yang ◽  
Mu-Yi Hua ◽  
Kuo-Chen Wei
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Therapeutic Agent ◽  
Brain Barrier ◽  
Term Survival ◽  
Blood Brain ◽  
The Brain

Malignant glioma is a severe primary CNS cancer with a high recurrence and mortality rate. The current strategy of surgical debulking combined with radiation therapy or chemotherapy does not provide good prognosis, tumor progression control, or improved patient survival. The blood-brain barrier (BBB) acts as a major obstacle to chemotherapeutic treatment of brain tumors by severely restricting drug delivery into the brain. Because of their high toxicity, chemotherapeutic drugs cannot be administered at sufficient concentrations by conventional delivery methods to significantly improve long-term survival of patients with brain tumors. Temporal disruption of the BBB by microbubble-enhanced focused ultrasound (FUS) exposure can increase CNS-blood permeability, providing a promising new direction to increase the concentration of therapeutic agents in the brain tumor and improve disease control. Under the guidance and monitoring of MR imaging, a brain drug-delivery platform can be developed to control and monitor therapeutic agent distribution and kinetics. The success of FUS BBB disruption in delivering a variety of therapeutic molecules into brain tumors has recently been demonstrated in an animal model. In this paper the authors review a number of critical studies that have demonstrated successful outcomes, including enhancement of the delivery of traditional clinically used chemotherapeutic agents or application of novel nanocarrier designs for actively transporting drugs or extending drug half-lives to significantly improve treatment efficacy in preclinical animal models.

Novel Phospholipid-Based Labrasol Nanomicelles Loaded Flavonoids for Oral Delivery with Enhanced Penetration and Anti-Brain Tumor Efficiency

2020 ◽  
Vol 17 (3) ◽  
pp. 229-245
Author(s):  
Gang Wang ◽  
Junjie Wang ◽  
Rui Guan
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Oral Delivery ◽  
Safe Delivery ◽  
Drug Delivery Vehicles ◽  
Therapeutic Benefits ◽  
Delivery Vehicles ◽  
The Brain

Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.

A Review of Various Machine Learning Techniques for Brain Tumor Detection from MRI Images

2020 ◽  
Vol 16 (8) ◽  
pp. 937-945
Author(s):  
Aaishwarya Sanjay Bajaj ◽  
Usha Chouhan
Keyword(s):  
Machine Learning ◽  
Brain Tumor ◽  
Ct Scan ◽  
Imaging Techniques ◽  
Critical Evaluation ◽  
Tumor Detection ◽  
Machine Learning Techniques ◽  
X Rays ◽  
Detection Techniques ◽  
The Brain

Background: This paper endeavors to identify an expedient approach for the detection of the brain tumor in MRI images. The detection of tumor is based on i) review of the machine learning approach for the identification of brain tumor and ii) review of a suitable approach for brain tumor detection. Discussion: This review focuses on different imaging techniques such as X-rays, PET, CT- Scan, and MRI. This survey identifies a different approach with better accuracy for tumor detection. This further includes the image processing method. In most applications, machine learning shows better performance than manual segmentation of the brain tumors from MRI images as it is a difficult and time-consuming task. For fast and better computational results, radiology used a different approach with MRI, CT-scan, X-ray, and PET. Furthermore, summarizing the literature, this paper also provides a critical evaluation of the surveyed literature which reveals new facets of research. Conclusion: The problem faced by the researchers during brain tumor detection techniques and machine learning applications for clinical settings have also been discussed.

Brain Tumor Detection via Asymmetry Quantification across Mid Sagittal Plane

2020 ◽  
Vol 13 ◽  
Author(s):  
Shoaib Amin Banday ◽  
Mohammad Khalid Pandit
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Sagittal Plane ◽  
Early Stage ◽  
Imaging Techniques ◽  
Complex Structure ◽  
Magnetic Resonance Images ◽  
Absolute Difference ◽  
Brain Hemispheres ◽  
The Brain

Introduction: Brain tumor is among the major causes of morbidity and mortality rates worldwide. According to National Brain Tumor Foundation (NBTS), the death rate has nearly increased by as much as 300% over last couple of decades. Tumors can be categorized as benign (non-cancerous) and malignant (cancerous). The type of the brain tumor significantly depends on various factors like the site of its occurrence, its shape, the age of the subject etc. On the other hand, Computer Aided Detection (CAD) has been improving significantly in recent times. The concept, design and implementation of these systems ascend from fairly simple ones to computationally intense ones. For efficient and effective diagnosis and treatment plans in brain tumor studies, it is imperative that an abnormality is detected at an early stage as it provides a little more time for medical professionals to respond. The early detection of diseases has predominantly been possible because of medical imaging techniques developed from past many decades like CT, MRI, PET, SPECT, FMRI etc. The detection of brain tumors however, has always been a challenging task because of the complex structure of the brain, diverse tumor sizes and locations in the brain. Method: This paper proposes an algorithm that can detect the brain tumors in the presence of the Radio-Frequency (RF) inhomoginiety. The algorithm utilizes the Mid Sagittal Plane as a landmark point across which the asymmetry between the two brain hemispheres is estimated using various intensity and texture based parameters. Result: The results show the efficacy of the proposed method for the detection of the brain tumors with an acceptable detection rate. Conclusion: In this paper, we have calculated three textural features from the two hemispheres of the brain viz: Contrast (CON), Entropy (ENT) and Homogeneity (HOM) and three parameters viz: Root Mean Square Error (RMSE), Correlation Co-efficient (CC), and Integral of Absolute Difference (IAD) from the intensity distribution profiles of the two brain hemispheres to predict any presence of the pathology. First a Mid Sagittal Plane (MSP) is obtained on the Magnetic Resonance Images that virtually divides brain into two bilaterally symmetric hemispheres. The block wise texture asymmetry is estimated for these hemispheres using the above 6 parameters.

Intracranial Tumors- Overview, Histological Types, Symptoms and Treatment Plans

2021 ◽  
Vol 11 (10) ◽  
pp. 133-144
Author(s):  
Dipak Chaulagain ◽  
Volodymyr Smolanka ◽  
Andriy Smolanka
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Marital Status ◽  
Size Variation ◽  
Intracranial Tumors ◽  
Regional Center ◽  
East And Southeast Asia ◽  
Abnormal Cells ◽  
Treatment Plans ◽  
The Brain

People, in general, are affected by a brain or intracranial tumor when abnormal cells started functioning within their brain. This paper explores mainly tumors that affect the brain. Almost every type of brain tumor might create symptoms which are based on the parts of the brain affected. In order to better understand reasons of occurrence intracranial tumors in various sections of the population, the study examined the relationship between sociodemographic variables, i.e., age, gender and marital status and the relative frequency of intracranial tumors as part of a study. Samples are collected based on the information from Uzhhorod Regional Center of Neurosurgery and Neurology in Ukraine. And factors such as age, gender and marital status has been considered to examine tumor size variation. The ratios of organ cancers in Ukrainians are evidently increasing. Besides, there has been growing trend in affected rates in both the genders of CNS cancers have been noticed in all the records. The ratio of most harmful brain tumors is comparatively in minimal ratio in East and Southeast Asia, and India. On the other hand, the highest ratio has been noted in European countries and as well United States, and Ukraine is one of those countries. The major burdens of cancer frequency in Ukraine have been noticed in the lung, breast, and prostate and brain. Of these, brain tumor rate in Ukraine had been hardly studied. The major difference in frequency in Asian and European populations implies the potential influence of genetic or environmental factors in malignant brain tumors. Continuing monitoring of tumor ratio in Ukraine is essential to comprehend how best to reduce cancer burden globally and to explain the causes of provincial variations, for example access to diagnosis methods and ecological exposures. Key words: Intracranial tumors, symptoms, tumor incidence in Ukraine, treatment plans, survival rate of cancer in Ukraine.

scholarly journals Pharmacodynamic Analysis of Magnetic Resonance Imaging-Monitored Focused Ultrasound-Induced Blood-Brain Barrier Opening for Drug Delivery to Brain Tumors

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Po-Chun Chu ◽  
Wen-Yen Chai ◽  
Han-Yi Hsieh ◽  
Jiun-Jie Wang ◽  
Shiaw-Pyng Wey ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Small Molecule ◽  
Focused Ultrasound ◽  
Therapeutic Agents ◽  
Tumor Treatment ◽  
Target Region ◽  
Pharmacodynamic Analysis ◽  
The Brain ◽  
Bbb Opening

Microbubble-enhanced focused ultrasound (FUS) can enhance the delivery of therapeutic agents into the brain for brain tumor treatment. The purpose of this study was to investigate the influence of brain tumor conditions on the distribution and dynamics of small molecule leakage into targeted regions of the brain after FUS-BBB opening. A total of 34 animals were used, and the process was monitored by 7T-MRI. Evans blue (EB) dye as well as Gd-DTPA served as small molecule substitutes for evaluation of drug behavior. EB was quantified spectrophotometrically. Spin-spin (R1) relaxometry and area under curve (AUC) were measured by MRI to quantify Gd-DTPA. We found that FUS-BBB opening provided a more significant increase in permeability with small tumors. In contrast, accumulation was much higher in large tumors, independent of FUS. The AUC values of Gd-DTPA were well correlated with EB delivery, suggesting that Gd-DTPA was a good indicator of total small-molecule accumulation in the target region. The peripheral regions of large tumors exhibited similar dynamics of small-molecule leakage after FUS-BBB opening as small tumors, suggesting that FUS-BBB opening may have the most significant permeability-enhancing effect on tumor peripheral. This study provides useful information toward designing an optimized FUS-BBB opening strategy to deliver small-molecule therapeutic agents into brain tumors.

scholarly journals Kinetic Analysis of 2-[11C]Thymidine PET Imaging Studies of Malignant Brain Tumors: Compartmental Model Investigation and Mathematical Analysis

2002 ◽  
Vol 1 (3) ◽  
pp. 153535002002021
Author(s):  
Joanne M. Wells ◽  
David A. Mankoff ◽  
Mark Muzi ◽  
Finbarr O'Sullivan ◽  
Janet F. Eary ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Cellular Proliferation ◽  
Compartment Model ◽  
Response To Therapy ◽  
Model Parameters ◽  
Normal Brain ◽  
Identifiability Analysis ◽  
Pet Tracer ◽  
Thymidine Transport

2-[11C]Thymidine (TdR), a PET tracer for cellular proliferation, may be advantageous for monitoring brain tumor progression and response to therapy. We previously described and validated a five-compartment model for thymidine incorporation into DNA in somatic tissues, but the effect of the blood–brain barrier on the transport of TdR and its metabolites necessitated further validation before it could be applied to brain tumors. Methods: We investigated the behavior of the model under conditions experienced in the normal brain and brain tumors, performed sensitivity and identifiability analysis to determine the ability of the model to estimate the model parameters, and conducted simulations to determine whether it can distinguish between thymidine transport and retention. Results: Sensitivity and identifiability analysis suggested that the non-CO2 metabolite parameters could be fixed without significantly affecting thymidine parameter estimation. Simulations showed that K1t and KTdR could be estimated accurately ( r = .97 and .98 for estimated vs. true parameters) with standard errors < 15%. The model was able to separate increased transport from increased retention associated with tumor proliferation. Conclusion: Our model adequately describes normal brain and brain tumor kinetics for thymidine and its metabolites, and it can provide an estimate of the rate of cellular proliferation in brain tumors.

Brain Tumor Reporting and Data System: A Pictorial Review

Neurographics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 175-185
Author(s):  
B. Rao ◽  
I. Ikuta ◽  
A. Mahajan ◽  
A.A. Karam ◽  
V.M. Zohrabian
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Response To Therapy ◽  
Data System ◽  
Imaging Features ◽  
New Paradigm ◽  
Advantages And Disadvantages ◽  
Pictorial Review ◽  
Almost All ◽  
The Brain

Brain tumors are a diverse group of neoplasms that are a source of substantial morbidity and mortality worldwide. Primary gliomas constitute almost all malignant brain tumors, with the most aggressive as well as most common form in adults, grade IV glioma or glioblastoma multiforme, carrying an especially poor prognosis. Neuroimaging is critical not only in the identification of CNS tumor but also in treatment-planning and assessing the response to therapy. Structured reporting continues to gain traction in radiology by reducing report ambiguity and improving consistency, while keeping referring clinicians and patients informed. The Brain Tumor Reporting and Data System (BT-RADS) is a relatively new paradigm that attempts to simplify and maximize consistency in radiologic reporting. BT-RADS incorporates MR imaging features, clinical assessment, and timing of therapy to assign each study a score or category, which is, in turn, linked to a management suggestion. The purpose of this pictorial review article is to familiarize radiologists and nonradiology neurologic specialists alike with BT-RADS, highlighting both advantages and limitations, in the hope that adoption of this system might ultimately facilitate more effective communication and improve consistency among reports.Learning Objective: To describe the features and underscore the advantages and disadvantages of the Brain Tumor Reporting and Data System (BT-RADS), a relatively new classification system that attempts to simplify and maximize consistency in radiologic reporting

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