MR Image Changes of Normal-Appearing Brain Tissue after Radiotherapy

Radiotherapy is part of the standard treatment of most primary brain tumors. Large clinical target volumes and physical characteristics of photon beams inevitably lead to irradiation of surrounding normal brain tissue. This can cause radiation-induced brain injury. In particular, late brain injury, such as cognitive dysfunction, is often irreversible and progressive over time, resulting in a significant reduction in quality of life. Since 50% of patients have survival times greater than six months, radiation-induced side effects become more relevant and need to be balanced against radiation treatment given with curative intent. To develop adequate treatment and prevention strategies, the underlying cause of radiation-induced side-effects needs to be understood. This paper provides an overview of radiation-induced changes observed in normal-appearing brains measured with conventional and advanced MRI techniques and summarizes the current findings and conclusions. Brain atrophy was observed with anatomical MRI. Changes in tissue microstructure were seen on diffusion imaging. Vascular changes were examined with perfusion-weighted imaging and susceptibility-weighted imaging. MR spectroscopy revealed decreasing N-acetyl aspartate, indicating decreased neuronal health or neuronal loss. Based on these findings, multicenter prospective studies incorporating advanced MR techniques as well as neurocognitive function tests should be designed in order to gain more evidence on radiation-induced sequelae.

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A comprehensive preclinical assessment of late-term imaging markers of radiation-induced brain injury

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz012 ◽

2019 ◽

Vol 1 (1) ◽

Cited By ~ 1

Author(s):

Tien T Tang ◽

Janice A Zawaski ◽

Shelli R Kesler ◽

Christine A Beamish ◽

Wilburn E Reddick ◽

...

Keyword(s):

Brain Tumor ◽

Brain Injury ◽

Side Effects ◽

Morphological Changes ◽

Gray Matter Volume ◽

Image Features ◽

Functional Markers ◽

Tumor Treatment ◽

Radiation Induced ◽

Imaging Markers

Abstract Background Cranial radiotherapy (CRT) is an important part of brain tumor treatment, and although highly effective, survivors suffer from long-term cognitive side effects. In this study we aim to establish late-term imaging markers of CRT-induced brain injury and identify functional markers indicative of cognitive performance. Specifically, we aim to identify changes in executive function, brain metabolism, and neuronal organization. Methods Male Sprague Dawley rats were fractionally irradiated at 28 days of age to a total dose of 30 Gy to establish a radiation-induced brain injury model. Animals were trained at 3 months after CRT using the 5-choice serial reaction time task. At 12 months after CRT, animals were evaluated for cognitive and imaging changes, which included positron emission tomography (PET) and magnetic resonance imaging (MRI). Results Cognitive deficit with signs of neuroinflammation were found at 12 months after CRT in irradiated animals. CRT resulted in significant volumetric changes in 38% of brain regions as well as overall decrease in brain volume and reduced gray matter volume. PET imaging showed higher brain glucose uptake in CRT animals. Using MRI, irradiated brains had an overall decrease in fractional anisotropy, lower global efficiency, increased transitivity, and altered regional connectivity. Cognitive measurements were found to be significantly correlated with six image features that included myelin integrity and local organization of the neural network. Conclusions These results demonstrate that CRT leads to late-term morphological changes, reorganization of neural connections, and metabolic dysfunction. The correlation between imaging markers and cognitive deficits can be used to assess late-term side effects of brain tumor treatment and evaluate efficacy of new interventions.

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The Emerging Role of miRNAs for the Radiation Treatment of Pancreatic Cancer

Cancers ◽

10.3390/cancers12123703 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3703

Author(s):

Lily Nguyen ◽

Daniela Schilling ◽

Sophie Dobiasch ◽

Susanne Raulefs ◽

Marina Santiago Franco ◽

...

Keyword(s):

Pancreatic Cancer ◽

Radiation Treatment ◽

Neoadjuvant Treatment ◽

Blood Biomarkers ◽

Curative Intent ◽

Treatment Regimens ◽

Tumor Bearing ◽

Radiation Induced ◽

Induced Changes

Today, pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide with a five-year overall survival rate of less than 7%. Only 15–20% of patients are eligible for curative intent surgery at the time of diagnosis. Therefore, neoadjuvant treatment regimens have been introduced in order to downsize the tumor by chemotherapy and radiotherapy. To further increase the efficacy of radiotherapy, novel molecular biomarkers are urgently needed to define the subgroup of pancreatic cancer patients who would benefit most from radiotherapy. MicroRNAs (miRNAs) could have the potential to serve as novel predictive and prognostic biomarkers in patients with pancreatic cancer. In the present article, the role of miRNAs as blood biomarkers, which are associated with either radioresistance or radiation-induced changes of miRNAs in pancreatic cancer, is discussed. Furthermore, the manuscript provides own data of miRNAs identified in a pancreatic cancer mouse model as well as radiation-induced miRNA changes in the plasma of tumor-bearing mice.

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Cognitive Decline Secondary to Therapeutic Brain Radiation—Similarities and Differences to Traumatic Brain Injury

Brain Sciences ◽

10.3390/brainsci9050097 ◽

2019 ◽

Vol 9 (5) ◽

pp. 97 ◽

Cited By ~ 1

Author(s):

Andrew Jonathan Huang ◽

David Kornguth ◽

Steven Kornguth

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Radiation Treatment ◽

The Elderly ◽

Whole Brain Radiation ◽

Major Interest ◽

Brain Barrier Permeability ◽

Radiation Induced ◽

Brain Radiation ◽

Collaborative Efforts

Traumatic brain injury (TBI) resulting from forceful impacts on the torso and head has been of major interest because of the prevalence of such injuries in military personnel, contact sports and the elderly. Cognitive and behavioral changes associated with TBI are also seen following whole brain radiation treatment for cancer and chemotherapy for disseminated tumors. The biological mechanisms involved in the initiation of TBI from impact, radiation, and chemotherapy to loss of cognitive function have several shared characteristics including increases in blood brain barrier permeability, blood vessel density, increases in inflammatory and autoimmune responses, alterations in NMDA and glutamate receptor levels and release of proteins normally sequestered in the brain into the blood and spinal fluid. The development of therapeutic agents that mitigate the loss of cognition and development of behavioral disorders in patients experiencing radiation-induced injury may provide benefit to those with TBI when similar processes are involved on a cellular or molecular level. Increased collaborative efforts between the radiation oncology and the neurology and psychiatry communities may be of major benefit for the management of brain injury from varied environmental insults.

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Position of Probe Determines Prognostic Information of Brain Tissue PO2 in Severe Traumatic Brain Injury

Neurosurgery ◽

10.1227/neu.0b013e31824ce933 ◽

2012 ◽

Vol 70 (6) ◽

pp. 1492-1503 ◽

Cited By ~ 45

Author(s):

Lucido L. Ponce ◽

Shibu Pillai ◽

Jovany Cruz ◽

Xiaoqi Li ◽

H. Julia ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Brain Tissue ◽

Severe Traumatic Brain Injury ◽

Neurological Outcome ◽

Normal Brain ◽

Probe Position ◽

Tissue Po2 ◽

The Relationship ◽

Abnormal Brain

Abstract BACKGROUND: Monitoring brain tissue PO2 (PbtO2) is part of multimodality monitoring of patients with traumatic brain injury (TBI). However, PbtO2 measurement is a sampling of only a small area of tissue surrounding the sensor tip. OBJECTIVE: To examine the effect of catheter location on the relationship between PbtO2 and neurological outcome. METHODS: A total of 405 patients who had PbtO2 monitoring as part of standard management of severe traumatic brain injury were studied. The relationships between probe location and resulting PbtO2 and outcome were examined. RESULTS: When the probe was located in normal brain, PbtO2 averaged 30.8 ± 18.2 compared with 25.6 ± 14.8 mm Hg when placed in abnormal brain (P < .001). Factors related to neurological outcome in the best-fit logistic regression model were age, PbtO2 probe position, postresuscitation motor Glasgow Coma Scale score, and PbtO2 trend pattern. Although average PbtO2 was significantly related to outcome in univariate analyses, it was not significant in the final logistic model. However, the interaction between PbtO2 and probe position was statistically significant. When the PbtO2 probe was placed in abnormal brain, the average PbtO2 was higher in those with a favorable outcome, 28.8 ± 12.0 mm Hg, compared with those with an unfavorable outcome, 19.5 ± 13.7 mm Hg (P = .01). PbtO2 and outcome were not related when the probe was placed in normal-appearing brain. CONCLUSION: These results suggest that the location of the PbtO2 probe determines the PbtO2 values and the relationship of PbtO2 to neurological outcome.

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Urinary isoprostanes as markers of radiation-induced normal brain injury

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2004.07.207 ◽

2004 ◽

Vol 60 (1) ◽

pp. S363-S364

Author(s):

T.M. Muanza ◽

S. Basu ◽

C.N. Coleman ◽

P. Tofilon ◽

K. Camphausen

Keyword(s):

Brain Injury ◽

Normal Brain ◽

Radiation Induced

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Metabolic alterations: A biomarker for radiation-induced normal brain injury-an MR spectroscopy study

Journal of Magnetic Resonance Imaging ◽

10.1002/jmri.21657 ◽

2009 ◽

Vol 29 (2) ◽

pp. 291-297 ◽

Cited By ~ 46

Author(s):

P.C. Sundgren ◽

V. Nagesh ◽

A. Elias ◽

C. Tsien ◽

L. Junck ◽

...

Keyword(s):

Brain Injury ◽

Mr Spectroscopy ◽

Normal Brain ◽

Spectroscopy Study ◽

Metabolic Alterations ◽

Radiation Induced

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The effects of anti-angiogenic therapy on the formation of radiation-induced microbleeds in normal brain tissue of patients with glioma

Neuro-Oncology ◽

10.1093/neuonc/nov128 ◽

2015 ◽

Vol 18 (1) ◽

pp. 87-95 ◽

Cited By ~ 16

Author(s):

Janine M. Lupo ◽

Annette M. Molinaro ◽

Emma Essock-Burns ◽

Nicholas Butowski ◽

Susan M. Chang ◽

...

Keyword(s):

Brain Tissue ◽

Normal Brain ◽

Normal Brain Tissue ◽

Angiogenic Therapy ◽

Radiation Induced

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Progress in the Pathogenesis and Treatment of Radiation-Induced Brain Injury

Proceedings of Anticancer Research ◽

10.26689/par.v4i6.1678 ◽

2020 ◽

Vol 4 (6) ◽

Author(s):

Xiaohan Gao ◽

Xiaohan Wu ◽

Xiaoqian Yang ◽

Shaoshui Chen ◽

Hongmin Zhi

Keyword(s):

Radiation Therapy ◽

Brain Injury ◽

Malignant Tumors ◽

Treatment Options ◽

Normal Brain ◽

Human Beings ◽

Whole Brain Radiation ◽

Radiation Induced ◽

Pass Through ◽

Effects Of Radiation

Malignant tumors are one of the serious public health problems that threaten the survival time of human beings. They are prone to metastasis to distant organs and the central nervous system is one of the common target organs. As it is difficult for chemotherapeutics, targeted drugs and other macromolecules to pass through the blood brain barrier (BBB), local radiation therapy is often used for treating intracranial primary or metastatic tumors. However, whether it is whole brain radiation therapy (WBRT) or stereotactic body radiation therapy (SBRT), the choice of radiation dose is limited by the side effects of radiation therapy on the surrounding normal brain tissues. Radiation-induced brain injury (RBI) can further develop into radiation necrosis (RN) in the late stage. Bevacizumab is often effective against RBI by antagonizing vascular endothelial growth factor (VEGF), but it still cannot completely reverse RN. Emerging treatment options such as human pluripotent stem-cell transplantation have made it possible to reverse the process of RN.

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