scholarly journals P11.37 Evaluating water content and electrical properties at 200 kHz in brain and GBM tumor tissue of three TTFields patients with conventional imaging

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii51-iii51
Author(s):  
Z Bomzon ◽  
C Wenger ◽  
H K Hershkovich ◽  
C Tempel Brami ◽  
M Giladi
Keyword(s):  
White Matter ◽  
Electrical Properties ◽  
Water Content ◽  
Brain Tissue ◽  
Gray Matter ◽  
Tumor Tissue ◽  
Specific Treatment ◽  
Patient Specific ◽  
Tissue Samples ◽  
Human Gbm

Abstract BACKGROUND Electrical properties (EPs) of brain tissue, specifically brain tumors, crucially determine the field distribution of Tumor Treating Fields (TTFields), an anti-mitotic treatment approved for glioblastoma multiforme (GBM). Due to the correlation of TTFields efficacy and field intensity at the tumor region, the knowledge of EPs in each patient is of great importance for patient-specific planning of treatment. Water content electrical properties tomography (wEPT) is a non-invasive imaging technique using water content (WC) maps obtained from rapidly acquired and processed conventional sequences to estimate the EPs of brain tissue at 128 MHz. The WC maps of this approach are constructed from two spin echo sequences similar to a T1 and a PD image. Following previous studies in rat tumor models demonstrating promising wEPT mapping of EPs in the brain at 200, this study examines the feasibility of this approach in human GBM patients. MATERIAL AND METHODS For three patients of the EF-14 trial population, we divided T1 and PD images pixel-by-pixel to obtain the image ratio. Using a transfer function, WC maps were generated and maps of the electrical conductivity σ and the relative permittivity ε r at 200 kHz were calculated with two different equations. RESULTS The median value of estimated WC remains similar in healthy brain tissues among all patients, ~73.5% in the white matter, ~82% in the gray matter. The median values of wEPT-estimated σ at 200 kHz in the white matter is ~0.09 S/m and in the gray matter ~0.18 S/m, corresponding median values of ε r at 200 kHz are ~2100 and ~3000 in white and gray matter respectively. Contrary, in the tumor the spread between the median values of WC and EPs is much higher. Stating the most important findings, in the necrosis median WC are 90.3%, 92.3%, 85.2% in patients 1–3 respectively with corresponding median σ values of 0.494, 0.657, 0.25 S/m. In the enhancing tumor the spread of median WC is even higher (67.2%, 83.6%, 85.5%), yet lower spread but also very heterogeneous median σ values of 0.075 S/m, 0.208, 0.259 S/m are estimated with wEPT. CONCLUSION Our results demonstrate the adaption of wEPT for mapping of WC and EPs at 200 kHz in three human GBM patients. In contrast to the vastly irregular tumor tissue, our estimations in healthy brain tissue are similar between patients and in accordance with EPs experimentally measured during our animal experiments and consistent with reported values in the literature. Hence, wEPT is a promising, fast technique based on regular MRI that might help patient-specific treatment planning of TTFields therapy, although the mapping of tumor tissue needs further confirmation in a greater population and investigations of EPs of excised tumor tissue samples should be conducted.

Multi-analyte liquid biopsies based treatment in advanced refractory cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15623-e15623
Author(s):  
Sewanti Limaye ◽  
Darshana Patil ◽  
Dadasaheb B Akolkar ◽  
Timothy Crook ◽  
Anantbhushan Ranade ◽  
...  
Keyword(s):  
Treatment Response ◽  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Single Gene ◽  
Objective Response ◽  
Specific Treatment ◽  
Patient Specific ◽  
Solid Organ ◽  
Liquid Biopsies ◽  
Blood Draw

e15623 Background: Tumor tissue profiling following invasive biopsies is presently the standard approach for indication-based therapy management in solid organ cancers. However, challenges in biopsy are traditionally described due to proximity to vital organs, or patients’ co-morbidities or unwillingness for an invasive procedure. Liquid biopsies for evaluation of cancers are also largely restricted to single gene testing for selection of targeted therapy agents. We developed a comprehensive liquid biopsy based multi-analyte (molecular and functional) investigation of the cancer (eLBx: Encyclopedic Liquid Biopsy) for selection and management of individualised treatments in a cohort of advanced refractory cancers. Methods: We obtained 20 mL blood from 65 patients with solid organ cancers where the disease had progressed following failure of at least two lines of systemic therapies and where biopsy to obtain tumor tissue for molecular profiling of tumor was unviable. Cell free tumor DNA (ctDNA) was interrogated for mutations, while exosomal mRNA was profiled for gene expression. Viable circulating tumor associated cells (C-TACs) were tested in vitro for chemoresistance and used to determine expression of cell surface signalling receptors by immunocytochemistry (ICC). The findings were integrated to generate patient-specific treatment regimens. In patients who received treatment, response was determined radiologically. Results: Fifty-one patients received eLBx-guided personalized treatments with combinations of cytotoxic, targeted and endocrine agents. No two patients received the same treatment regimen. Forty-three patients were evaluable for treatment response per protocol among whom Partial Response (PR) was observed in 14 patients yielding an Objective Response Rate (ORR) of 32.6%. Additionally, 23 patients showed Stable Disease thus yielding an overall Disease Control rate of 86.1%. Median Progression Free Survival (PFS) was 108 days. There were no Grade IV therapy related Adverse Events or therapy related deaths. Conclusions: The ability to make informed treatment choices from a convenient blood draw implies a reduced dependence on invasive biopsies for disease management. We demonstrate successful management of advanced refractory solid tumor malignancies using an integrational non-invasive multi-analyte liquid biopsy approach. Clinical trial information: CTRI/2019/02/017548.

Cerebral Distribution of Immunoconjugate after Treatment for Neoplastic Meningitis Using an Intrathecal Radiolabeled Monoclonal Antibody

Neurosurgery ◽  
1989 ◽  
Vol 25 (2) ◽  
pp. 253-258 ◽  
Author(s):  
Jonathan Charles Benjamin ◽  
Timothy Moss ◽  
Robin Peter Mosely ◽  
Ruth Maxwell ◽  
Hugh Beresford Coakham
Keyword(s):  
Monoclonal Antibody ◽  
White Matter ◽  
Brain Stem ◽  
Tumor Cells ◽  
Gray Matter ◽  
Tumor Tissue ◽  
Autoradiographic Study ◽  
Neoplastic Meningitis ◽  
Antibody Binding ◽  
Carcinomatous Meningitis

Abstract A detailed autopsy and autoradiographic study was performed after the death of a patient undergoing intrathecal, antibody-guided irradiation for carcinomatous meningitis. The results demonstrated tumor cells infiltrating the surface meninges and a severe astrocytic reaction associated with oedema in the periventricular and brain stem subpial white matter. This was not seen in cortical or other gray matter structures. Autoradiographic examination correlated well, demonstrating isotope within the oedematous areas of the white matter in addition to the expected concentration in the leptomeningeal layers. These findings are discussed in the context of antibody binding to tumor tissue and the possible benefits conferred in the treatment of infiltrating tumor cells.

scholarly journals Probabilistic comparison of gray and white matter coverage between depth and surface intracranial electrodes in epilepsy: a patient-specific modeling and empirical study

2021 ◽  
Author(s):  
Daria Nesterovich Anderson ◽  
Chantel M Charlebois ◽  
Elliot H Smith ◽  
Amir M Arain ◽  
Tyler S Davis ◽  
...  
Keyword(s):  
White Matter ◽  
Electric Fields ◽  
Gray Matter ◽  
Patient Specific ◽  
Surface Electrodes ◽  
University Of Utah ◽  
Depth Electrodes ◽  
Patient Specific Modeling ◽  
Intracranial Recording ◽  
Intracranial Electrodes

Objective. The objective of this study is to quantify the coverage of gray and white matter during intracranial electroencephalography in a cohort of epilepsy patients with surface and depth electrodes. Methods. We included 65 patients with strip electrodes (n=12), strip and grid electrodes (n=24), strip, grid, and depth electrodes (n=7), or depth electrodes only (n=22) from the University of Utah spanning 2010-2020. Patient-specific imaging was used to generate probabilistic gray and white matter maps and atlas segmentations. The gray and white matter coverage was quantified based on spherical volumes centered on electrode centroids, with radii ranging from 1-15 mm, along with detailed finite element models of local electric fields Results. Gray matter coverage was highly dependent on the chosen radius of influence (RoI). Using a 2.5 mm RoI, depth electrodes covered more gray matter than surface electrodes; however, surface electrodes covered more gray matter at RoI larger than 4 mm. White matter coverage was greatest for depth electrodes at all RoIs, which is noteworthy for studies involving stimulation mapping. Depth electrodes were able to record significantly more gray matter from the amygdala and hippocampus than subdural electrodes. Significance. This study provides the first probabilistic analysis to quantify gray and white matter coverage for multiple categories of intracranial recording configurations. Depth electrodes may offer increased per contact coverage of gray matter over other recording strategies if the desired signals are local to the contact, while subdural grids and strips can sample more gray matter if the desired signals are more diffuse.

Measurement of Glioma Viscoelasticity Using a Handheld Palpation Imitation Device

2017 ◽  
Author(s):  
Shigeto Hayashi ◽  
Atsushi Sakuma ◽  
Takashi Sasayama ◽  
Eiji Kohmura
Keyword(s):  
Computed Tomography ◽  
Brain Tumor ◽  
Elastic Modulus ◽  
White Matter ◽  
Gray Matter ◽  
Tumor Tissue ◽  
Viscoelastic Behavior ◽  
En Bloc ◽  
Tomography Image ◽  
Computed Tomography Image

We examined glioma tissues immediately after en-bloc removal during surgery and measured elastic modulus, viscosity, and viscoelasticity of the gray and white matter to confirm the feasibility of measurement using an indentation device. Measurements were obtained from excised parenchymal brain tumor tissue of four adult patients. The white matter exhibited higher elastic modulus than the gray matter in all patients. Viscoelasticity analysis was performed in two patients, with viscoelastic behavior observed in the white but not in the gray matter in both patients. The loss of viscoelasticity in the white matter observed in one patient may be related to the calcification visible in the preoperative computed tomography image.

scholarly journals Probabilistic comparison of gray and white matter coverage between depth and surface intracranial electrodes in epilepsy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daria Nesterovich Anderson ◽  
Chantel M. Charlebois ◽  
Elliot H. Smith ◽  
Amir M. Arain ◽  
Tyler S. Davis ◽  
...  
Keyword(s):  
White Matter ◽  
Electric Fields ◽  
Gray Matter ◽  
Patient Specific ◽  
Finite Element Models ◽  
Surface Electrodes ◽  
Depth Electrodes ◽  
Intracranial Recording ◽  
Intracranial Electrodes ◽  
Intracranial Electroencephalography

AbstractIn this study, we quantified the coverage of gray and white matter during intracranial electroencephalography in a cohort of epilepsy patients with surface and depth electrodes. We included 65 patients with strip electrodes (n = 12), strip and grid electrodes (n = 24), strip, grid, and depth electrodes (n = 7), or depth electrodes only (n = 22). Patient-specific imaging was used to generate probabilistic gray and white matter maps and atlas segmentations. Gray and white matter coverage was quantified using spherical volumes centered on electrode centroids, with radii ranging from 1 to 15 mm, along with detailed finite element models of local electric fields. Gray matter coverage was highly dependent on the chosen radius of influence (RoI). Using a 2.5 mm RoI, depth electrodes covered more gray matter than surface electrodes; however, surface electrodes covered more gray matter at RoI larger than 4 mm. White matter coverage and amygdala and hippocampal coverage was greatest for depth electrodes at all RoIs. This study provides the first probabilistic analysis to quantify coverage for different intracranial recording configurations. Depth electrodes offer increased coverage of gray matter over other recording strategies if the desired signals are local, while subdural grids and strips sample more gray matter if the desired signals are diffuse.

scholarly journals Widespread distribution of the major polypeptide component of MAP 1 (microtubule-associated protein 1) in the nervous system.

1984 ◽  
Vol 98 (1) ◽  
pp. 320-330 ◽  
Author(s):  
G S Bloom ◽  
T A Schoenfeld ◽  
R B Vallee
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Cerebral Cortex ◽  
White Matter ◽  
Rat Brain ◽  
Brain Tissue ◽  
Gray Matter ◽  
Neuronal Morphology ◽  
Double Labeling ◽  
Brain And Spinal Cord

We prepared a monoclonal antibody to microtubule-associated protein 1 (MAP 1), one of the two major high molecular weight MAP found in microtubules isolated from brain tissue. We found that MAP 1 can be resolved by SDS PAGE into three electrophoretic bands, which we have designated MAP 1A, MAP 1B, and MAP 1C in order of increasing electrophoretic mobility. Our antibody recognized exclusively MAP 1A, the most abundant and largest MAP 1 polypeptide. To determine the distribution of MAP 1A in nervous system tissues and cells, we examined tissue sections from rat brain and spinal cord, as well as primary cultures of newborn rat brain by immunofluorescence microscopy. Anti-MAP 1A stained white matter and gray matter regions, while a polyclonal anti-MAP 2 antibody previously prepared in this laboratory stained only gray matter. This confirmed our earlier biochemical results, which indicated that MAP 1 is more uniformly distributed in brain tissue than MAP 2 (Vallee, R.B., 1982, J. Cell Biol., 92:435-442). To determine the identity of cells and cellular processes immunoreactive with anti-MAP 1A, we examined a variety of brain and spinal cord regions. Fibrous staining of white matter by anti-MAP 1A was generally observed. This was due in part to immunoreactivity of axons, as judged by examination of axonal fiber tracts in the cerebral cortex and of large myelinated axons in the spinal cord and in spinal nerve roots. Cells with the morphology of oligodendrocytes were brightly labeled in white matter. Intense staining of Purkinje cell dendrites in the cerebellar cortex and of the apical dendrites of pyramidal cells in the cerebral cortex was observed. By double-labeling with antibodies to MAP 1A and MAP 2, the presence of both MAP in identical dendrites and neuronal perikarya was found. In primary brain cell cultures anti-MAP 2 stained predominantly cells of neuronal morphology. In contrast, anti-MAP 1A stained nearly all cells. Included among these were neurons, oligodendrocytes and astrocytes as determined by double-labeling with anti-MAP 1A in combination with antibody to MAP 2, myelin basic protein or glial fibrillary acidic protein, respectively. These results indicate that in contrast to MAP 2, which is specifically enriched in dendrites and perikarya of neurons, MAP 1A is widely distributed in the nervous system.

Experimental Carbon Dioxide Laser Brain Lesions and Intracranial Dynamics: Part 2

Neurosurgery ◽  
1985 ◽  
Vol 16 (4) ◽  
pp. 454-457
Author(s):  
Ernesto G. Tiznado ◽  
Hector E. James ◽  
Susan Moore
Keyword(s):  
Carbon Dioxide ◽  
White Matter ◽  
Water Content ◽  
Gray Matter ◽  
Carbon Dioxide Laser ◽  
Brain Lesions ◽  
Brain Water Content ◽  
The Impact ◽  
The Brain ◽  
Brain Water

Abstract Experimental brain lesions were created over the left parietooccipital cortex of the albino rabbit through the intact dura mater with high radiating carbon dioxide laser energy (40-W impact, 0.5-second duration, for a total time of 4 seconds on a 12.5-mm surface). The brain water content was studied 2, 6, and 24 hours after the insult. Another two groups of animals received acute therapy with either dexamethasone (1 mg/kg) or furosemide (1 mg/kg). In all groups, Evans blue extravasation uniformly extended from the impact crater into the surrounding white matter. The brain water content in the gray matter was elevated from the control value by 2 hours after impact (P < 0.005) and remained elevated at 6 and 24 hours. The white matter brain water content did not increase until 6 hours after impact and remained elevated in the 24-hour group (P < 0.005). After dexamethasone treatment, there was a significant decrease of water in the gray matter (P < 0.01), but not in the white matter. With furosemide therapy, there was no reduction of gray or white matter brain water.

The determination of brain water content: microgravimetry versus drying-weighing method

1982 ◽  
Vol 57 (1) ◽  
pp. 99-107 ◽  
Author(s):  
Taku Shigeno ◽  
Mario Brock ◽  
Shuku Shigeno ◽  
Emanuel Fritschka ◽  
Jorge Cervós-Navarro
Keyword(s):  
White Matter ◽  
Water Content ◽  
Brain Edema ◽  
Brain Tissue ◽  
Brain Water Content ◽  
Automatic Production ◽  
Wide Range ◽  
Weighing Method ◽  
Brain Water

✓ The microgravimetric technique and the drying-weighing method for the determination of brain water content are analyzed and compared. A new method has been devised for the automatic production of the gradient column. For gravimetry, tissue samples weighing more than 30 mg have proven adequate for measurement. Specific gravity (SG) should be determined as early as 1 minute after tissue is inserted into the gradient column. Calculations of cerebral blood volume (CBV) from changes in SG of both brain tissue and intravascular perfusate have shown that the SG of brain tissue is considerably influenced by changes in CBV. This is because the SG of blood is higher than that of brain tissue, and may lead to a decrease of SG of about 0.002 in anemic cortex and of 0.001 in anemic white matter, which will simulate a false increase in tissue volume as water of 4% and 2%, respectively. This methodological error may be relevant when the early stages of ischemic brain edema development are studied. Water content of brain tissue can also be determined with acceptable accuracy by vacuum freeze-drying samples of brain tissue weighing about 100 mg. In contrast to cortex, white matter shows a wide range of individual and regional differences in water content. Thus, conclusions on the presence of brain edema drawn from tissue water determinations should always be subjected to cautious analysis and criticism.

Alterations in the Distribution of Water, Sodium, Potassium, and Chloride in Brain during the Evolution of Ischemic Cerebral Edema

Neurosurgery ◽  
1978 ◽  
Vol 3 (2) ◽  
pp. 187-195 ◽  
Author(s):  
Alfonso M. Bremer ◽  
Charles R. West ◽  
Yamada Kazuo
Keyword(s):  
White Matter ◽  
Cerebral Ischemia ◽  
Water Content ◽  
Gray Matter ◽  
Cerebral Edema ◽  
Focal Cerebral Ischemia ◽  
Late Phase ◽  
Subcortical White Matter ◽  
Sodium Potassium ◽  
Morphological Studies

Abstract Experimental regional cerebral ischemia in the territory of the middle cerebral artery (MCA) in a primate (Macaca mulatta) was produced by selective embolization of the internal carotid artery bifurcation. Determinations of tissue dry weight (percentage) and tissue sodium, potassium, and chloride on samples from the affected and contralateral hemispheres were carried out periodically until 48 hours after the onset of focal cerebral ischemia. Samples from the cortex supplied by the occluded MCA showed excesses in water content, increases in sodium, and decreases in potassium as early as 3 to 4 hours after occlusion. Hemispheric swelling became apparent after 4 to 5 hours, with obvious “gray matter edema.” However, only minimal to moderate increases in the water content of the subcortical white matter (without change in electrolytes) were observed in the same brain sections. Subcortical white matter samples from the affected MCA territory showed gradual increases in water content at 12, 24, and 48 hours, but definite increases in sodium and decreases in potassium were not observed until 24 to 48 hours of ischemia. During this late phase, the “gray matter edema” remained unchanged or underwent partial resolution. Our results agree with data derived from morphological studies suggesting that ischemic cerebral edema develops in a diphasic fashion, with a primary phase of early “gray matter edema” evolving to a secondary phase of late “white matter edema.”

scholarly journals NIMG-41. RAPID AND ACCURATE CREATION OF PATIENT-SPECIFIC COMPUTATIONAL MODELS FOR GBM PATIENTS RECEIVING OPTUNE THERAPY WITH CONVENTIONAL IMAGING (T1w/PD)

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi170-vi170 ◽  
Author(s):  
Cornelia Wenger ◽  
Hadas Sara Hershkovich ◽  
Catherine Tempel-Brami ◽  
Moshe Giladi ◽  
Ze’ev Bomzon
Keyword(s):  
Water Content ◽  
Computational Models ◽  
Specific Treatment ◽  
Mixture Theory ◽  
Specific Model ◽  
Patient Specific ◽  
Great Promise ◽  
Head Model ◽  
Tissue Segmentation ◽  
Binary Segmentation

Abstract BACKGROUND For understanding the electric field distributions in glioblastoma (GBM) patients receiving OptuneTM therapy computational head models are employed. Accurate and fast model creation is of high importance to patient-specific treatment planning for improving efficacy, i.e., for maximizing intensity delivered to the tumor which depends on the tissues’ electric properties (EPs). Traditional model creation relies on time-consuming tissue segmentation and troublesome binary categorization of distinct tumor areas for assigning homogenous EPs. Here, we present a feasibility study of a new approach for fast model creation that uses individually created, heterogeneous EP maps from conventional MRIs. METHODS In a previous animal study we adapted water-content based electrical properties tomography (wEPT) for creating electrical conductivity (σ) maps at 200 kHz, the operating frequency of OptuneTM therapy. This adapted wEPT approach uses a T1w and a PD image to map the tissues’ water-content (WC) with a simple function. Subsequently the σ map is calculated as a function of WC based on Maxwell’s mixture theory. Three patients of the EF-14 trial were selected for calculating WC and σ maps. One patient was chosen to create a computational head model for simulating OptuneTM treatment. RESULTS The wEPT-estimated values of WC and σ in the healthy brain are accurate, homogenous and consistent among patients. Contrary, wEPT-estimates of WC and σ in tumor tissues are very heterogeneous and variable between patients. The patient-specific model with wEPT reveals more detailed current pathways during OptuneTM therapy. CONCLUSIONS The results emphasize the need for individual head model creation, since binary segmentation masks with pre-defined σ values are not recommended for the heterogeneous and variable tumor. The presented approach holds great promise for rapid creation of patient-specific computational models because only conventional MRIs are needed. However, this method needs to be validated and further established with analyzing more patients.

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