Role of Cerebrospinal Fluid (CSF) Flow Imaging in Evaluating Distribution of Infused Agents from the 4th Ventricle to the Total Spine in Treatment of Recurrent Posterior Fossa Malignant Neoplasms   Session ID: eP-4 Sub-Session ID: eP-165 Rajan Patel, MD; Clarke Sitton, MD; M Kerr, RN; Stephen Fletcher, DO; Manish Shah, MD; David Sandberg, MD, FAANS, FACS, FAAP

DISCLOSURE None.

INTRODUCTION Malignant neoplasms such as medulloblastoma, ATRT, ependymoma account for 50% of posterior fossa/infratentorial pediatric brain tumors. Approximately 50% of these patients will have leptomeningeal spread at time of presentation. Initial treatment options include Surgery, Craniospinal Radiation +/- Chemotherapy. Survival rates are very poor in these patients when tumor recur after initial treatment.

PURPOSE This IRB approved study is based upon the hypothesis that infusion of chemotherapy agents directly into the fourth ventricle may offer an effective new treatment approach for children with recurrent, infratentorial malignant brain tumors. Infusion into the 4th ventricle will also enable drug distribution within the spinal subarachnoid space and help treat leptomeningeal dissemination of the tumor in the brain and spine.

PURPOSE Disadvantages: Traditionally the CSF flow distribution is assessed by nuclear medicine CSF flow study after injection of 111 In-DTPA into spinal canal by lumbar puncture. Disadvantages: Invasive procedure Radiation Poor spatial resolution with lack of anatomic information.

MATERIAL AND METHODS Cine phase contrast CSF flow MRI imaging of total spine was used to assess noninvasively the distribution of the infused chemotherapy agent from the fourth ventricle down to the lumbar spine. 6 patients with a median age of 12 years who had previously undergone a posterior fossa craniotomy for maximal safe surgical resection of a recurrent tumor and implantation of a 4th ventricular access device (Ommaya Reservoir).

MATERIAL AND METHODS Prior to infusing chemotherapy into the 4th ventricle, all patients underwent non-invasive Cine phase contrast CSF flow MRI sequence of the brain and total spine with Velocity Encoding (VENC) of 5 cm/sec and 10 cm/sec to confirm CSF flow from the fourth ventricular outlets to the cervical, thoracic, and lumbar spine. CSF flow was assessed by two fellowship trained neuroradiologists and was characterized qualitatively as present or absent as well as any obstruction in CSF flow.

Phase Contrast CSF Flow Sequence Acquisition FOV 450 Sagittal body coil locator of Entire spine slice thickness 5mm, 0 mm gap FOV 450 Coronal body coil locator of Entire spine slice thickness 5mm, 0 mm gap FOV 380 x 314 Sagittal CSF Flow 1 Slice, slice thickness 5mm, 0mm gap. Check images for any artifacts appear in the cord. Placement of the anterior SAT band as close as possible to spine to reduce heart motion and other artifacts that may fall into the field of the CSF flow as seen in next slide. FOV is set according to patient size.

Phase Contrast CSF Flow Sequence Acquisition Sagittal Locator : Patient is placed on a Entire Spine/CTL (Cervical, Thoracic, Lumbar) coil. Sagittal Locator is acquired in 2 Stages and then fused. Coronal plane is then Acquired to check for spine alignment.

Phase Contrast CSF Flow Sequence Acquisition Sagittal Locator : Sagittal Sat Band is placed anterior to the spine to saturate out the pulsation artifacts from Heart as well as Aorta.

Phase Contrast CSF Flow Sequence Acquisition Coronal Locator : Coronal plane is then acquired to check for spine alignment. Sagittal Single Line placement is setup up from coronal plane.

Phase Contrast CSF Flow Sequence Parameters 2D Plane Sagittal VENC 5 cm/sec or 10 cm/sec FOV 20 - 36 depending upon patient size TR 20 - 24 TE 4 - 6 Flip Angle 10 - 12 Matrix 250 x 250 Slice Thickness / Gap 5mm / 0 Scan Time 5 – 6 mins

6 year, male pt. with recurrent medulloblastoma DWI ADC T1 Post T2 isointense mass within left sided posterior fossa resection cavity with associated restricted diffusion and post contrast enhancement. Finding suggestive of recurrent medulloblastoma.

6 year, male pt. with recurrent medulloblastoma T1 Post T2 Patient underwent resection of recurrent medulloblastoma and placement of Ommaya reservoir with catheter ends within resection cavity.

6 year, male pt. with recurrent medulloblastoma Whole Spine Cine Phase Gated CSF flow sequence demonstrates preservation of CSF flow from 4th ventricle to lumbar spine. Typically, white represents caudal to cranial flow, and black represents cranial to caudal flow.

RESULTS All 6 patients demonstrated CSF flow from the 4th ventricle to the cervical, thoracic, and lumbar spine with no evidence of obstruction. All sets of images were of diagnostic quality and there was excellent concordance between the two neuroradiologists in their interpretation. Preliminary results of this study (n=6) demonstrated stable disease in 4 patients, improvement in 1 patients and disease progression in 1 patient on follow up MRIs.

Physics of Phase Contrast-MRI Until now, the only MR imaging technique to visualize CSF movement is cardiac gated cine phase contrast MR sequence (PC-MRI). The PC MRI generates signal contrast between flowing and stationary nuclei by sensitizing the phase of the transverse magnetization to the velocity of motion. Two data sets are acquired with opposite sensitization/polarity.

Physics of Phase Contrast-MRI When the 2 datasets are subtracted, accumulated net phase of stationary nuclei will be zero and signal will be eliminated from final image. However moving nuclei move from one position in the magnetic field gradient to another during the time between the executions of the 2 opposite polarity gradients, the moving nuclei accumulate a net phase proportional to the velocity of the nuclei and there is residual signal from flowing CSF in final image. http://mriquestions.com/phase-contrast.html

Physics of Phase Contrast-MRI Before PC MRI data are acquired, the anticipated maximum CSF flow velocity must be entered into the pulse sequence protocol which is known as “Velocity encoding(VENC)”. VENC can be adjusted according to the arrangement of the bipolar gradients. PC generates the best results when maximum CSF flow velocity should be the same as, or slightly less than, the selected VENC. Flow velocities greater than the VENC produce aliasing artifacts, and velocities much smaller than the VENC result in poor image quality and weak signal.

Physics of Phase Contrast-MRI CSF flow is pulsatile and synchronous with the cardiac cycle, therefore cardiac gating can be used to provide increased sensitivity. Cardiac gating can be provided with two different methods: prospective gating and retrospective gating. In retrospective gating, the entire cardiac cycle is sampled while in prospective gating only small portion of cardiac cycle is sampled. Results from retrospective gating are more accurate as compared with prospective gating.

Physics of Phase Contrast-MRI Phase contrast CSF flow sequence contains magnitude and phase information. Magnitude images provide anatomical information. Phase images provides velocity information. Greyscale intensity of each pixel is directly related to the velocity of CSF.

Study Interpretation CSF pulsations are driven by the cardiac cycle. During systole, blood rushes into the fixed-volume cranium, squeezing the ventricles, and causing CSF to flow caudally out of the brain into the spine and spinal cord. During diastole, CSF flows cranially back into the brain. Caudal flow of CSF is conventionally represented as shades of white on phase images, whereas cranial flow is by shades of black.

Study Interpretation (A) (B) (C) Re-phased image is a magnitude of flow compensated signal, in this image the flow is bright and background is visible Magnitude image is a magnitude of difference signal, in this image the flow is bright and the background is suppressed Phase image is a phase of difference signal, in this image forward flow is bright, reverse flow is black and background is mid-grey.

CONCLUSION CSF flow including the fourth ventricle and the total spine can be assessed non-invasively with CINE phase contrast CSF flow sequence. This sequence can be served as a new alternative to nuclear medicine studies for confirmation of CSF flow before infusion of intrathecal chemotherapy. Advantages over nuclear medicine studies include avoiding an invasive procedure as well as radiation exposure.

REFERENCES Mbonane S, Andronikou S. Interpretation and value of MR CSF flow studies for paediatric neurosurgery. South African Journal of Radiology. 2013;17 Battal B, Kocaoglu M, Bulakbasi N et-al. Cerebrospinal fluid flow imaging by using phase-contrast MR technique. Br J Radiol. 2011;84 (1004): 758-65 Yildiz H, Yazici Z, Hakyemez B, Erdogan C, Parlak M. Evaluation of CSF flow patterns of posterior fossa cystic malformations using CSF flow MR imaging. Neuroradiology 2006;48:595–605 Yildiz H, Erdogan C, Yalcin R, Yazici Z, Hakyemez B, Parlak M, et al. Evaluation of communication between intracranial arachnoid cysts and cisterns with phase-contrast cine MR imaging. AJNR Am J Neuroradiol 2005;26:145–51

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