Comparison of Abnormal Cortical Development in Brain Malformations on Postmortem Imaging With Autopsy - Full Text View

Sponsored by:	The Hospital for Sick Children
Information provided by:	The Hospital for Sick Children
ClinicalTrials.gov Identifier:	NCT00686530

Purpose

Examination of the fetal brain at autopsy is technically challenging because of marked fragility of the brain tissue. Studies have found postmortem fetal MR to be particularly useful in examining gross structural abnormalities in fetal brain and spine. We have recently included postmortem MR as part of the radiological studies for fetal autopsy workup. Using the same MR data, the development of normal layering of the brain, also called laminar organization, can also be assessed. This laminar organization of the brain is often disturbed in congenital malformations. Our aim is to study the disturbance in laminar organization of the postmortem brain with MR, using structural MR and a type of MR sequence called diffusion tensor imaging, which is well suited for assessing the organization of the developing brain. The postmortem MR findings will be compared with gold standard of histopathology. This will help us understand the abnormal development of gray and white matter in brain malformations. Knowledge gained from studying the abnormal laminar organization in brain malformations will serve as a reference for future studies of fetal brain malformations in-utero using MRI.

Condition	Intervention
Brain Malformation	Procedure: MR Imaging Procedure: Autopsy

U.S. FDA Resources

Study Type:	Observational
Study Design:	Case Control, Prospective
Official Title:	Comparison of Abnormal Cortical Development in Brain Malformations on Postmortem Imaging With Autopsy

Further study details as provided by The Hospital for Sick Children:

Biospecimen Retention: Samples With DNA

Biospecimen Description:

Macroscopic examination of the fetus will be performed initially follwed by organ removal for tissue fixation for a period of two weeks.

Estimated Enrollment:	40
Study Start Date:	August 2007
Estimated Study Completion Date:	February 2010
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
1	Procedure: MR Imaging Postmortem MR will be included as part of the autopsy examination in cases of suspected brain malformations. Imaging will be done using 1.5T GE CV/I MRI magnet. The specimen is scanned, following fixation, using an 8-channel head coil or 8-channel knee coil, depending on the size of the brain. Structural postmortem MR will include spin-echo T1, axial SPGR, and T2 imaging in three planes. Diffusion tensor imaging will be performed in the coronal plane. Procedure: Autopsy Autopsy will be performed according to accepted standards, based on clinical indications. Macroscopic examination of the fetus will be performed initially , followed by organ removal for tissue fixation for a period of two weeks.

Groups/Cohorts

Assigned Interventions

1

Procedure: MR Imaging

Postmortem MR will be included as part of the autopsy examination in cases of suspected brain malformations. Imaging will be done using 1.5T GE CV/I MRI magnet. The specimen is scanned, following fixation, using an 8-channel head coil or 8-channel knee coil, depending on the size of the brain. Structural postmortem MR will include spin-echo T1, axial SPGR, and T2 imaging in three planes. Diffusion tensor imaging will be performed in the coronal plane.

Procedure: Autopsy

Autopsy will be performed according to accepted standards, based on clinical indications. Macroscopic examination of the fetus will be performed initially , followed by organ removal for tissue fixation for a period of two weeks.

Detailed Description:

Autopsy will be performed at Mount Sinai Hospital according to accepted current standards, based on clinical indications. Macroscopic examination of the fetus will be performed initially, followed by organ removal for tissue fixation for a period of two weeks. The brain is then scanned with MRI at the Hospital for Sick Children. The brain is transported in an air-tight container containing 10% formalin and sealed with paraffin lined tape. All brains will be anonymised and coded with a number prior to MRI examination. Following MR imaging, the tissue will be examined, sampled and reported in the usual fashion at Mount Sinai Hospital.
Postmortem MR will be included as part of the autopsy examination in cases of suspected brain malformations. Postmortem MR will be performed at the Hospital for Sick Children due to availability of expertise in postmortem neuroimaging and imaging will be done using 1.5T GE CV/I MRI magnet (General Electric, Milwaukee, WI). Postmortem MR will be performed following dissection and tissue fixation to avoid any unnecessary delay in tissue fixation. The specimen will be scanned in an air-tight container containing formalin 10%, sealed with paraffin lined tape. Structural postmortem MR will include coronal spin-echo T1 (TR=517msec, TE=10msec, FOV=18cm, slice thickness=20-30mm, matrix=320x256), axial SPGR (TR=23msec, TE=8msec, FOV=18cm, slice thickness=1.1mm, matrix=256x256) and T2 imaging in three planes (TR=4115msec, TE=115msec, FOV=16cm, slice thickness=20-30mm, matrix=320x256). Diffusion tensor imaging (TR=8300msec, TE=99msec, FOV=180mm, slice thickness=2-3mm, b=700mm/sec2, NEX=8, matrix=128x128, 25 directions) will be performed in the coronal plane to match the histological sections of brain tissue in autopsy.
Analysis. The laminar organization of the fetal cerebrum on structural MR and diffusion tensor imaging will be evaluated. In particular, the germinal matrix, intermediate zone, subplate and cortex will be assessed. This will be compared with the gold standard of histopathology. The presence or absence of corticospinal tracts will also be assessed and compared with macroscopic examination and histological sections.
Statistical analysis. The sensitivity, specificity and accuracy of postmortem MR, both structural and diffusion tensor imaging, as compared to the gold standard of autopsy in assessing the abnormal laminar organization of fetal cerebrum will be evaluated.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

40 fetal post mortem brains, with suspected diagnosis of brain malformation

Criteria

Inclusion Criteria:

suspected antenatal diagnosis of brain malformation who will undergo autopsy and MRI to further assess the malformations
above 18 weeks gestation

Exclusion Criteria:

significant autolysis of tissue specimens prior to tissue fixation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00686530

Contacts

Contact: Wendy Doda

416-813-1922

wendy.doda@sickkids.ca

Locations

Canada, Ontario
The Hospital for Sick Children	Not yet recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Wendy Doda 416-813-1922 wendy.doda@sickkids.ca
Principal Investigator: Susan Blaser, MD
Sub-Investigator: Elysa Widjaja, MD
Sub-Investigator: Patrick Shannon, MD
Mount Sinai Hospital	Recruiting
Toronto, Ontario, Canada, M5G 1X5

Sponsors and Collaborators

The Hospital for Sick Children

Investigators

Principal Investigator:

Susan Blaser

The Hospital for Sick Children

More Information

Responsible Party:	The Hospital for Sick Children ( Susan Blaser/Principal Investigator )
Study ID Numbers:	1000011050
Study First Received:	May 23, 2008
Last Updated:	May 23, 2008
ClinicalTrials.gov Identifier:	NCT00686530
Health Authority:	Canada: Ethics Review Committee

Keywords provided by The Hospital for Sick Children:

Fetal Death
Magnetic Resonance Imaging
Autopsy
Telencephalon
Pyramidal Tracts

Study placed in the following topic categories:

Death
Congenital Abnormalities
Fetal Death

ClinicalTrials.gov processed this record on January 16, 2009