Effect of therapeutic ionizing radiation on the human brain

Abstract

We test a hypothesis that fractionated radiation therapy within a therapeutic dose range is associated with a dose-related change in normal brain, detectable by quantitative magnetic resonance imaging. A total of 33 patients were examined by quantitative magnetic resonance imaging to measure brain tissue spin-lattice relaxation time (T1) before treatment, and at various times during and after radiation therapy. A T1 map was generated at each time point, and radiation therapy isodose contours were superimposed on the corresponding segmented T1 map. Changes in white matter and gray matter T1 were analyzed as a function of radiation therapy dose and time since treatment, controlling for patient age and tumor site. In white matter, a dose level of more than 20 Gy was associated with a dose-dependent decrease in T1 over time, which became significant 6 months after treatment. There was no significant change in T1 of gray matter over time, at radiation therapy doses of less than 60 Gy. However, GM in close proximity to the tumor had a lower T1 before therapy. Our results represent the first radiation dose-response data derived from pediatric brain in vivo. These findings confirm that white matter is more vulnerable to radiation-induced change than is gray matter, and suggest that T1 mapping is sensitive to radiation-related changes over a broad dose range (20 to 60 Gy). Human white matter T1 is not sensitive to radiation therapy of less than 20 Gy, and gray matter T1 is unchanged over the dose range used to treat human brain tumor. The reduction of gray matter T1 near the tumor could result from compression of cortical parenchyma near the growing tumor mass, or from tumor cell invasion directly into the parenchyma. If brain T1 is a surrogate for radiation effect, reducing the volume of normal white matter receiving more than 20 Gy could be an important treatment planning goal.

Neuroanatomical target theory as a predictive model for radiation-induced cognitive decline

“…At 10 Gy, neural stem cells number is significantly reduced, and by 40 Gy white matter disease is prominent. 15,16 The 60 Gy dose combined parameters of tumor location, risk of necrosis, 1,2 and dose. We determined neuroanatomical target structures and what dose threshold predicted functional decline after receiving RT.…”

Hippocampus avoidance with fan beam and volumetric arc radiotherapy for base of skull tumours

“…Barani et al have postulated the dose tolerance of the neural stem cells compartments, including the hippocampus, to be in the range of 10À20 Gy 9,10 and this corresponds to clinical observations of a threshold for neurocognitive side effects and MRI changes when doses exceed 18À20 Gy. 19 Gutiérrez et al in comparison set objectives of keeping the dose to the entire hippocampi less than 6 Gy, recognising the Figure 3. (a) Composite doseÀvolume histograms of the PTV and organs at risk for plans with a 10 mm GTV to PTV margin for helical tomotherapy (HT10; blue solid), co-planar volumetric arc (RA_1; red dots), non-coplanar 2 arc (RA_2; green dash), and non-coplanar 3 arc techniques (RA_3; blue dash).…”

“…In comparison, a standard, coplanar three field pituitary plan or non-hippocampus sparing coplanar intensity modulated arc delivery might be expected to deliver doses of 20À25 Gy to the hippocampi (Figure 1), in excess of the doses postulated to result in stem cell loss and neurocognitive changes. 12,16,19 The coplanar nature of the skull base and hippocampus creates challenges in sparing these structures without increasing brainstem or eye dose due to the limited numbers of in plane ''corridors'' to deliver dose to central tumours while simultaneously limiting dose to the surrounding OAR. This limitation applies to both HT and co-planar IMRT delivery techniques and has been noted by other authors.…”

“…11 Other authors have noted a threshold for neurocognitive side effects and MRI changes when doses exceed 18À20 Gy. 19 Thus dose metrics of D 5 , D 20 , D 50 , V 6Gy , and V 18Gy to both unilateral hippocampi and as a paired structure were analyzed. We also examined metrics for OARs including eyes and optic nerves.…”

Isolated Extramedullary Relapse in Childhood Acute Lymphocytic Leukemia

“…Thus, through the use of chemotherapy with superior efficacy in the CNS, patients with isolated CNS relapsed ALL can be treated adequately with reduced doses of CNS irradiation, and sometimes none at all. This modern approach to treatment can be expected to decrease the acute and/or late complications associated with cranial irradiation such as neurocognitive deficits, endocrinopathies, and second malignancy [13,[37][38][39].…”