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Hippocampal Contouring: A Contouring Atlas for RTOG 0933 Vinai Gondi, M. D. 1 Wolfgang Hippocampal Contouring: A Contouring Atlas for RTOG 0933 Vinai Gondi, M. D. 1 Wolfgang A. Tome, Ph. D. 1 Howard A. Rowley, M. D. 2 Minesh P. Mehta, M. D. 3 Departments of 1 Human Oncology and 2 Neuroradiology, University of Wisconsin Comprehensive Cancer Center 3 Department of Radiation Oncology, Northwestern University Feinberg School of Medicine 1

MRI-CT Fusion • MRI: – Three-dimensional spoiled gradient (3 D-SPGR) axial MRI scan of MRI-CT Fusion • MRI: – Three-dimensional spoiled gradient (3 D-SPGR) axial MRI scan of the head with standard axial and coronal FLAIR, axial T 2 -weighted and gadolinium contrast-enhanced T 1 -weighted sequence acquisitions. – 1. 25 mm slice thickness is preferred to contour the hippocampus accurately. Slice thickness of 1. 5 mm or less is permitted. – Obtain in supine position; immobilization devices used for CT simulation and daily radiation treatments not necessary. • CT Simulation: – Non-contrast treatment-planning CT scan of the entire head region. – 1. 25 -1. 5 mm slice thickness is preferred for accurate hippocampal sparing planning. Slice thickness of 2. 5 mm or less is permitted. – Immobilize patient in supine position using an immobilization device such as an Aquaplast mask over the head. Treat patients in the immobilization device. • MRI-CT Fusion: – Fuse the 3 D-SPGR MRI and the treatment-planning CT. 2

General Principles • Please note that we are not contouring the entire hippocampus, but General Principles • Please note that we are not contouring the entire hippocampus, but focusing mostly on the subgranular zone (SGZ) • Contour the hippocampus on T 1 -weighted MRI axial sequences. • Given the preponderance of gray matter in the hippocampus, focus contouring on the T 1 hypointense signal medial to the temporal horn. 3

Red: Hippocampus Temporal Horn Begin contouring at the most caudal (inferior) extent of the Red: Hippocampus Temporal Horn Begin contouring at the most caudal (inferior) extent of the crescentic-shaped floor of the temporal horn of the lateral ventricle and contour the hypointense grey matter located medial to the CSF hypointensity, not the white, bright white matter. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 4

Red: Hippocampus Fimbriae Continue contouring in a cephalad (superior) direction, medial to the temporal Red: Hippocampus Fimbriae Continue contouring in a cephalad (superior) direction, medial to the temporal horn of the lateral ventricle and contour the hypointense grey matter, not the white, bright white matter. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 5

Red: Hippocampus Fimbria Continue contouring in a cephalad (superior) direction. Avoid contouring the fimbriae, Red: Hippocampus Fimbria Continue contouring in a cephalad (superior) direction. Avoid contouring the fimbriae, the T 1 hyperintense structures located superomedial to the hippocampus. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 6

Red: Hippocampus Continue contouring in a cephalad (superior) direction, medial to the temporal horn Red: Hippocampus Continue contouring in a cephalad (superior) direction, medial to the temporal horn of the lateral ventricle and contour the hypointense grey matter, not the white, bright white matter. Note that the contours are progressively moving in a supero-posterior direction, keeping in line with the curved banana shaped structure of the hippocampus. Avoid the fimbriae and also avoid the grey matter (amygdala and uncus) located anterior to the tip of the temporal horn of the ventricles. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 7

Red: Hippocampus Amygdala Uncus As contouring proceeds postero-cranially, the anterior boundary of the hippocampus Red: Hippocampus Amygdala Uncus As contouring proceeds postero-cranially, the anterior boundary of the hippocampus is defined by the anterior edge of the temporal horn, to distinguish the hippocampus from the T 1 hypointense gray matter of the amygdala, lying anterior and superior to the hippocampus. The medial boundary of the hippocampus is defined by the “boomerang-shaped” uncus MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 8

Red: Hippocampus Uncal Recess Continue contouring in a cephalad (superior) direction, medial to the Red: Hippocampus Uncal Recess Continue contouring in a cephalad (superior) direction, medial to the temporal horn of the lateral ventricle and contour only the hypointense grey matter, not the white, bright white matter. Continue to avoid the fimbriae and also avoid the grey matter (amygdala and uncus) located anterior to the tip of the temporal horn of the ventricles. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 9

Red: Hippocampus Medial edge of Uncal recess. Recess Uncal The emergence of the uncal Red: Hippocampus Medial edge of Uncal recess. Recess Uncal The emergence of the uncal recess of the temporal horn defines the anterior boundary of the hippocampus. This may not be seen on all axial image sets due to its limited size. The medial boundary of the hippocampus becomes defined by the medial edge of the uncal recess. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 10

Red: Hippocampus Continue contouring in a cephalad (superior) direction, medial to the temporal horn Red: Hippocampus Continue contouring in a cephalad (superior) direction, medial to the temporal horn of the lateral ventricle and contour only the hypointense grey matter, not the white, bright white matter. Continue to avoid the fimbriae and also avoid the grey matter (amygdala and uncus) located anterior to the tip of the temporal horn of the ventricles. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 11

Red: Hippocampus Quadrageminal cistern Postero-cranially, the medial boundary of the hippocampus is defined by Red: Hippocampus Quadrageminal cistern Postero-cranially, the medial boundary of the hippocampus is defined by the lateral edge of the quadrageminal cistern which is the CSF containing space lateral to the pons. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 12

Red: Hippocampus Quadrageminal cistern Continue contouring in a cephalad (superior) direction; note that at Red: Hippocampus Quadrageminal cistern Continue contouring in a cephalad (superior) direction; note that at this level, the temporal horn of the lateral ventricle may no longer be visible on every slice, but the quadrigeminal cistern serves as a medial reference landmark. Contour only the hypointense grey matter, not the bright white matter. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 13

Red: Hippocampus Temporal horn of the lateral ventricle Quadrageminal cistern The hippocampus remains medial Red: Hippocampus Temporal horn of the lateral ventricle Quadrageminal cistern The hippocampus remains medial to the temporal horn of the lateral ventricle throughout its extent, and so on slices where you can visualize it, use it as a consistent reference. The quadrigeminal cistern remains a good medial landmark. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 14

Red: Hippocampus Temporal horn of the lateral ventricle Quadrageminal cistern The hippocampus remains medial Red: Hippocampus Temporal horn of the lateral ventricle Quadrageminal cistern The hippocampus remains medial to the temporal horn of the lateral ventricle throughout its extent, and so on slices where you can visualize it, use it as a consistent reference. The quadrigeminal cistern remains a good medial landmark. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 15

Red: Hippocampus Caudate Putamen Thalamus Quadrageminal cistern The hippocampal tail remains posterior to the Red: Hippocampus Caudate Putamen Thalamus Quadrageminal cistern The hippocampal tail remains posterior to the thalamus as it curves medially toward the splenium of the corpus callosum. Note that it is still medially located relative to the lateral ventricle. Also note that the thalamus, basal ganglia and internal capsule now become visible. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 16

Red: Hippocampus Internal Capsule The hippocampal tail remains posterior to the thalamus as it Red: Hippocampus Internal Capsule The hippocampal tail remains posterior to the thalamus as it curves medially toward the splenium of the corpus callosum. Note that it is still medially located relative to the lateral ventricle. Also note that the thalamus, basal ganglia and internal capsule now become visible. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 17

Red: Hippocampus Hippocampal tail Atrium of the lateral ventricle The postero-cranial extent of the Red: Hippocampus Hippocampal tail Atrium of the lateral ventricle The postero-cranial extent of the hippocampal tail is located just antero-medially to the atrium of the lateral ventricle. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 18

Red: Hippocampus Hippocampal tail Atrium of the lateral ventricle The postero-cranial extent of the Red: Hippocampus Hippocampal tail Atrium of the lateral ventricle The postero-cranial extent of the hippocampal tail is located just antero-medially to the atrium of the lateral ventricle. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 19

Red: Hippocampus Quadrageminal cistern Even in its cephalad (superior) extent, the hippocampal tail remains Red: Hippocampus Quadrageminal cistern Even in its cephalad (superior) extent, the hippocampal tail remains lateral to the lateral edge of the quadrageminal cistern. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 20

Red: Hippocampus Quadrageminal cistern Even in its cephalad (superior) extent, the hippocampal tail remains Red: Hippocampus Quadrageminal cistern Even in its cephalad (superior) extent, the hippocampal tail remains lateral to the lateral edge of the quadrageminal cistern. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 21

Red: Hippocampus Splenium Terminate hippocampal contours at the point where the T 1 -hypointense Red: Hippocampus Splenium Terminate hippocampal contours at the point where the T 1 -hypointense structure no longer borders the atrium of the lateral ventricle. At this point, the crux of the fornix emerges anteriorly and the splenium of the corpus callosum can be visualized posteriorly. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 22

Red: Hippocampus The grey signal from the hippocampus is no longer visible. Do not Red: Hippocampus The grey signal from the hippocampus is no longer visible. Do not contour any further. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 23

Red: Hippocampus Green: Hippocampal Avoidance Zone Generate the hippocampal avoidance zone using a 5 Red: Hippocampus Green: Hippocampal Avoidance Zone Generate the hippocampal avoidance zone using a 5 mm volumetric expansion on the hippocampus. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 24

Red: Hippocampus Green: Hippocampal Avoidance Zone Hippocampal 1) Tail 2) Body 3) Head Generate Red: Hippocampus Green: Hippocampal Avoidance Zone Hippocampal 1) Tail 2) Body 3) Head Generate the hippocampal avoidance zone using a 5 mm volumetric expansion on the hippocampus. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 25

Red: Hippocampus Green: Hippocampal Avoidance Zone Hippocampal 1) Tail 2) 1) Tail Body 2) Red: Hippocampus Green: Hippocampal Avoidance Zone Hippocampal 1) Tail 2) 1) Tail Body 2) Body 3) Head The hippocampus has three anatomic subdivisions: the head, body, and tail; note that the head is inferior or caudad, the body is superoposterior and the tail is most cephalad (superior) and posterior, and an overall “banana” shape emerges on sagittal images, located in the plane of the lateral ventricle. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 26

Red: Hippocampus Green: Hippocampal Avoidance Zone Hippocampal 1) Tail 2) Body 3) Head The Red: Hippocampus Green: Hippocampal Avoidance Zone Hippocampal 1) Tail 2) Body 3) Head The hippocampus has three anatomic subdivisions: the head, body, and tail; note that the head is inferior or caudad, the body is superoposterior and the tail is most cephalad (superior) and posterior, and an overall “banana” shape emerges on sagittal images, located in the plane of the lateral ventricle. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 27

Red: Hippocampus Green: Hippocampal Avoidance Zone Hippocampal 1) Tail 2) Body 3) Head Amygdala Red: Hippocampus Green: Hippocampal Avoidance Zone Hippocampal 1) Tail 2) Body 3) Head Amygdala On sagittal sections, confirm delineation of the hippocampus separate from neighboring structures, such as the amygdala. 28 MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998)

Red: Hippocampus Green: Hippocampal Avoidance Zone Hippocampal 1) Tail 2) Body 3) Head Amygdala Red: Hippocampus Green: Hippocampal Avoidance Zone Hippocampal 1) Tail 2) Body 3) Head Amygdala On sagittal sections, confirm delineation of the hippocampus separate from neighboring structures, such as the amygdala. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 29

Red: Hippocampus Green: Hippocampal Avoidance Zone Hippocampal 1) Tail 2) Body 3) Head Parahippocampal Red: Hippocampus Green: Hippocampal Avoidance Zone Hippocampal 1) Tail 2) Body 3) Head Parahippocampal Gyrus On coronal sections, confirm delineation of the hippocampus separate from neighboring structures, such as the parahippocampal gyrus, which has different signal intensity. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 30

Red: Hippocampus Green: Hippocampal Avoidance Zone Hippocampal 1) Tail 2) Body 3) Head Parahippocampal Red: Hippocampus Green: Hippocampal Avoidance Zone Hippocampal 1) Tail 2) Body 3) Head Parahippocampal Gyrus On coronal sections, confirm delineation of the hippocampus separate from neighboring structures, such as the parahippocampal gyrus, which has different signal intensity. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 31

Red: Hippocampus Hippocampal 1)Crus of the fornix Tail 2) Body 3) Head Green: Hippocampal Red: Hippocampus Hippocampal 1)Crus of the fornix Tail 2) Body 3) Head Green: Hippocampal Avoidance Zone Crus of the fornix On sagittal and coronal sections, confirm separation between the hippocampal tail and the crus of the fornix. Note the location of the hippocampii medial to the ventricles on the coronal images. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 32

Red: Hippocampus Green: Hippocampal Avoidance Zone Hippocampal 1) Tail 2) Body 3) Head On Red: Hippocampus Green: Hippocampal Avoidance Zone Hippocampal 1) Tail 2) Body 3) Head On sagittal and coronal sections, confirm separation between the hippocampal tail and the crus of the fornix. Note the location of the hippocampii medial to the ventricles on the coronal images. MR Images courtesy of: Holmes CJ, Hoge R, Collins L, et al. "Enhancement of MR Images Using Registration for Signal Averaging" Journal of Computer Assisted Tomography 22, 324 -333 (1998) 33