Comparison of Abnormal Cortical Development in Brain Malformations on Postmortem Imaging With Autopsy

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.

Study Overview

• Status: Withdrawn
• Conditions: Brain Malformation
• Intervention / Treatment: Procedure: MR Imaging; Procedure: Autopsy

Detailed Description

1. 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.
2. 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.
3. 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.
4. 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.

• Study Type: Observational

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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.

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Susan Blaser, The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Anticipated): August 1, 2009
• Study Completion (Anticipated): February 1, 2010

Study Registration Dates

• First Submitted: May 23, 2008
• First Submitted That Met QC Criteria: May 23, 2008
• First Posted (Estimate): May 30, 2008

Study Record Updates

• Last Update Posted (Estimate): December 3, 2013
• Last Update Submitted That Met QC Criteria: December 2, 2013
• Last Verified: May 1, 2008

More Information

Terms related to this study

• Keywords: Magnetic Resonance Imaging; Autopsy; Fetal Death; Telencephalon; Pyramidal Tracts
• Additional Relevant MeSH Terms: Nervous System Diseases; Congenital Abnormalities; Nervous System Malformations
• Other Study ID Numbers: 1000011050