Brain Tumor, Glioma, Neurofibromatosis Type 1
Conditions
Keywords
Brain, Cancer, Neurofibromatosis type 1, NF1, Magnetic resonance fingerprinting, MRF
Brief summary
This study will look at the feasibility of using magnetic resonance fingerprinting (MRF) in children, adolescents and young adults (AYA) with and without brain tumors. This study will also look at subjects with and without neurofibromatosis type 1(NF1), a genetic disorder that affects the growth of nervous system cells. Further, it will explore potential ways of using of MRF signal measurements in children, adolescents, and young adults with brain tumors, including tissue characterization, looking at whether the treatment was effective, and finding metastasized tumors of unknown origin (occult tumors). To explore the feasibility and potential applications of MRF, this study will recruit up to 80 subjects but will stop once 10 subjects have usable data in each of six groups.
Detailed description
Specific Aim 1: Demonstrate the feasibility of magnetic resonance fingerprinting (MRF) in children, adolescents and young adults (AYA) with and without brain tumors. Specific Aim 2: Characterize the MRF signature of low-grade gliomas Specific Aim 3: Determine whether MRF can identify occult tumor in subjects with low-grade glioma. Specific Aim 4: Determine whether MRF can identify treatment effects in low-grade gliomas. Specific Aim 5: Explore whether common brain tumors can be differentiated by comparing pre-operative MRF signature with pathologic diagnosis. Outline: This study will examine the feasibility of MRF in children and AYA and determine whether quantitative measures of T1 and T2 relaxation times can be derived in subjects \<35 years of age. Approximately 80 subjects will be evaluated and include subgroups where MRF may be of particular utility, including children and AYA subjects with brain tumors and subjects with neurofibromatosis type 1 (NF1). Additional aims will investigate the utility of MRF in these groups.
Interventions
DEVICEMagnetic Resonance Imaging
Patients will have a scan of soft tissue using magnetic field and radio frequency pulses.
Magnetic resonance fingerprinting (MRF) uses pseudo-randomized variation in acquisition parameters to generate a multi-parametric data signal that can be compared to signal patterns calculated from all possible combinations of parameters of interest. The closest match in signal patterns yields the parameters used to calculate the theoretical signal, in each voxel, and thus a map of all parameters of interest for that tissue. This process allows for rapid quantitation of MR relaxometry values (T1 and T2).
Sponsors
Case Comprehensive Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects undergoing MRI evaluation of the brain * NF1 status will be determined by clinical exam or genetic testing * NF1-associated Optic Pathway Glioma (OPG) will be defined as radiographic evidence of glioma along the optic nerve, chiasm, tract or radiation in a child with NF1 * Untreated low grade gliomas will be imaging-defined gliomas that have not yet been exposed to radiation or systemic chemotherapy. Those exposed to therapy will have had radiation and/or systemic chemotherapy more than 1 month prior to scans
Exclusion criteria
* History of mental retardation unrelated to brain tumor * Presence of a genetic disorder other than NF1 that effects cognition or is associated with MR imaging abnormalities (e.g. tuberous sclerosis) * History of cerebrovascular accident (stroke) * Birth weight below five pounds, premature birth prior to 36 weeks of gestation, or ischemic episode at birth * Major psychiatric diagnosis prior to neuro-oncological diagnosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Duration of MRF Sequence - Feasibility | Up to 1 year | The duration of MRF sequence in minutes will be recorded as a measure of feasibility |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Evaluable T1 and T2 Relaxation Times on MRF Scans | Up to 1 year | Number of patients which have evaluable scans at both T1 and T2 |
| Comparison of Relaxometry MRI Scans Between Low Grade Gliomas and Healthy Brain Tissue | Up to 1 year | Using Wilcoxon rank sum test to compare continuous variables, researchers will identify scans with significant difference in relaxometry between low-grade (composite of arms 1,3,4) and versus healthy brain tissue. |
| Combination of Relaxometry MRI Scans Between High Grade Gliomas and Healthy Brain Tissue | Up to 1 year | Using Wilcoxon rank sum test to compare continuous variables, researchers will identify scans with significant difference in relaxometry between high-grade (arm 6) and versus healthy brain tissue. |
| Comparison of Scans of Treated and Untreated Low Grade Gliomas (LGG) | Up to 1 year | Using paired t-tests or non-parametric Wilcoxon signed rank tests, researchers will identify scans with significant differences in scans of treated and untreated tumors |
Other
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Relaxometry Values Between Tumors of Varying Pathology | Up to 1 year | Descriptive statistics will be used to identify the T1 and T2 relaxation times for tumors of different types on pre-operative MRF scan |
Countries
United States
Participant flow
Pre-assignment details
Protocol enrollment was 35 but data are only available for 34 participants - Study team believes one participant's scan was never completed with MRF but because the study was terminated in 2018 with no further access to data this cannot be confirmed.
Participants by arm
| Arm | Count |
|---|---|
| NF1-associated Optic Pathway Glioma (OPG) Patients with neurofibromatosis type 1 (NF1) associated OPG will be imaged by magnetic resonance imaging and magnetic resonance fingerprinting
Magnetic Resonance Imaging: Patients will have a scan of soft tissue using magnetic field and radio frequency pulses.
Magnetic Resonance Fingerprinting: Magnetic resonance fingerprinting (MRF) uses pseudo-randomized variation in acquisition parameters to generate a multi-parametric data signal that can be compared to signal patterns calculated from all possible combinations of parameters of interest. The closest match in signal patterns yields the parameters used to calculate the theoretical signal, in each voxel, and thus a map of all parameters of interest for that tissue. This process allows for rapid quantitation of MR relaxometry values (T1 and T2). | 4 |
| NF1 Without Brain Tumor Patients with NF1 without brain tumor will be imaged by magnetic resonance imaging and magnetic resonance fingerprinting
Magnetic Resonance Imaging: Patients will have a scan of soft tissue using magnetic field and radio frequency pulses.
Magnetic Resonance Fingerprinting: Magnetic resonance fingerprinting (MRF) uses pseudo-randomized variation in acquisition parameters to generate a multi-parametric data signal that can be compared to signal patterns calculated from all possible combinations of parameters of interest. The closest match in signal patterns yields the parameters used to calculate the theoretical signal, in each voxel, and thus a map of all parameters of interest for that tissue. This process allows for rapid quantitation of MR relaxometry values (T1 and T2). | 6 |
| Without NF1 and With Brain Tumor Exposed to Therapy Patients without NF1 and with low grade gliomas exposed to therapy will be imaged by magnetic resonance imaging and magnetic resonance fingerprinting
Magnetic Resonance Imaging: Patients will have a scan of soft tissue using magnetic field and radio frequency pulses.
Magnetic Resonance Fingerprinting: Magnetic resonance fingerprinting (MRF) uses pseudo-randomized variation in acquisition parameters to generate a multi-parametric data signal that can be compared to signal patterns calculated from all possible combinations of parameters of interest. The closest match in signal patterns yields the parameters used to calculate the theoretical signal, in each voxel, and thus a map of all parameters of interest for that tissue. This process allows for rapid quantitation of MR relaxometry values (T1 and T2). | 6 |
| Without NF1 and With Untreated Low Grade Brain Tumors Patients without NF1 and with untreated low grade gliomas will be imaged by magnetic resonance imaging and magnetic resonance fingerprinting
Magnetic Resonance Imaging: Patients will have a scan of soft tissue using magnetic field and radio frequency pulses.
Magnetic Resonance Fingerprinting: Magnetic resonance fingerprinting (MRF) uses pseudo-randomized variation in acquisition parameters to generate a multi-parametric data signal that can be compared to signal patterns calculated from all possible combinations of parameters of interest. The closest match in signal patterns yields the parameters used to calculate the theoretical signal, in each voxel, and thus a map of all parameters of interest for that tissue. This process allows for rapid quantitation of MR relaxometry values (T1 and T2). | 8 |
| Without NF1 and Without Brain Tumors Patients without NF1 and without brain tumor will be imaged by magnetic resonance imaging and magnetic resonance fingerprinting
Magnetic Resonance Imaging: Patients will have a scan of soft tissue using magnetic field and radio frequency pulses.
Magnetic Resonance Fingerprinting: Magnetic resonance fingerprinting (MRF) uses pseudo-randomized variation in acquisition parameters to generate a multi-parametric data signal that can be compared to signal patterns calculated from all possible combinations of parameters of interest. The closest match in signal patterns yields the parameters used to calculate the theoretical signal, in each voxel, and thus a map of all parameters of interest for that tissue. This process allows for rapid quantitation of MR relaxometry values (T1 and T2). | 4 |
| Brain Tumors of Assorted Pathology Patients with brain tumors of assorted pathologies will be imaged by magnetic resonance imaging and magnetic resonance fingerprinting
Magnetic Resonance Imaging: Patients will have a scan of soft tissue using magnetic field and radio frequency pulses.
Magnetic Resonance Fingerprinting: Magnetic resonance fingerprinting (MRF) uses pseudo-randomized variation in acquisition parameters to generate a multi-parametric data signal that can be compared to signal patterns calculated from all possible combinations of parameters of interest. The closest match in signal patterns yields the parameters used to calculate the theoretical signal, in each voxel, and thus a map of all parameters of interest for that tissue. This process allows for rapid quantitation of MR relaxometry values (T1 and T2). | 6 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | NF1-associated Optic Pathway Glioma (OPG) | Total | Brain Tumors of Assorted Pathology | Without NF1 and Without Brain Tumors | Without NF1 and With Untreated Low Grade Brain Tumors | Without NF1 and With Brain Tumor Exposed to Therapy | NF1 Without Brain Tumor |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 4.5 Years | 15 Years | 14 Years | 12.5 Years | 15 Years | 14 Years | 17.5 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 34 Participants | 6 Participants | 4 Participants | 8 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 34 Participants | 6 Participants | 4 Participants | 8 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 4 participants | 34 participants | 6 participants | 4 participants | 8 participants | 6 participants | 6 participants |
| Sex: Female, Male Female | 2 Participants | 18 Participants | 0 Participants | 3 Participants | 6 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 16 Participants | 6 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 6 | 0 / 6 | 1 / 8 | 0 / 4 | 1 / 6 |
| other Total, other adverse events | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 4 | 0 / 6 |
| serious Total, serious adverse events | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 4 | 0 / 6 |
Outcome results
Primary
Average Duration of MRF Sequence - Feasibility
The duration of MRF sequence in minutes will be recorded as a measure of feasibility
Time frame: Up to 1 year
Population: Participants enrolled in study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NF1-associated Optic Pathway Glioma (OPG) | Average Duration of MRF Sequence - Feasibility | 11 minutes | Standard Deviation 0 |
| NF1 Without Brain Tumor | Average Duration of MRF Sequence - Feasibility | 11 minutes | Standard Deviation 0 |
| Without NF1 and With Brain Tumor Exposed to Therapy | Average Duration of MRF Sequence - Feasibility | 11 minutes | Standard Deviation 0 |
| Without NF1 and With Untreated Low Grade Brain Tumors | Average Duration of MRF Sequence - Feasibility | 11 minutes | Standard Deviation 0 |
| Without NF1 and Without Brain Tumors | Average Duration of MRF Sequence - Feasibility | 11 minutes | Standard Deviation 0 |
| Brain Tumors of Assorted Pathology | Average Duration of MRF Sequence - Feasibility | 11 minutes | Standard Deviation 0 |
Secondary
Combination of Relaxometry MRI Scans Between High Grade Gliomas and Healthy Brain Tissue
Using Wilcoxon rank sum test to compare continuous variables, researchers will identify scans with significant difference in relaxometry between high-grade (arm 6) and versus healthy brain tissue.
Time frame: Up to 1 year
Population: Participants in arm 6 had a measurable solid portion of HGG and were used for this analysis. Each participant had a single tumor sample measured and a single normal-appearing white matter measured.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NF1-associated Optic Pathway Glioma (OPG) | Combination of Relaxometry MRI Scans Between High Grade Gliomas and Healthy Brain Tissue | T1 | 1863 milliseconds (ms) | Standard Deviation 70 |
| NF1-associated Optic Pathway Glioma (OPG) | Combination of Relaxometry MRI Scans Between High Grade Gliomas and Healthy Brain Tissue | T2 | 91 milliseconds (ms) | Standard Deviation 13 |
| NF1 Without Brain Tumor | Combination of Relaxometry MRI Scans Between High Grade Gliomas and Healthy Brain Tissue | T1 | 979 milliseconds (ms) | Standard Deviation 156 |
| NF1 Without Brain Tumor | Combination of Relaxometry MRI Scans Between High Grade Gliomas and Healthy Brain Tissue | T2 | 45 milliseconds (ms) | Standard Deviation 7 |
Comparison: Comparison of T1 valuesp-value: 0.081Wilcoxon (Mann-Whitney)
Comparison: Comparison of T2 valuesp-value: 0.081Wilcoxon (Mann-Whitney)
Secondary
Comparison of Relaxometry MRI Scans Between Low Grade Gliomas and Healthy Brain Tissue
Using Wilcoxon rank sum test to compare continuous variables, researchers will identify scans with significant difference in relaxometry between low-grade (composite of arms 1,3,4) and versus healthy brain tissue.
Time frame: Up to 1 year
Population: Participants enrolled on arms 1,3 and 4. Combination of Arms 1, 3, and 4 for reporting was pre-specified in the study protocol. Each participant had a single tumor sample measured and a single normal-appearing white matter measured.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NF1-associated Optic Pathway Glioma (OPG) | Comparison of Relaxometry MRI Scans Between Low Grade Gliomas and Healthy Brain Tissue | T1 | 1355 milliseconds (ms) | Standard Deviation 187 |
| NF1-associated Optic Pathway Glioma (OPG) | Comparison of Relaxometry MRI Scans Between Low Grade Gliomas and Healthy Brain Tissue | T2 | 56 milliseconds (ms) | Standard Deviation 19 |
| NF1 Without Brain Tumor | Comparison of Relaxometry MRI Scans Between Low Grade Gliomas and Healthy Brain Tissue | T1 | 916 milliseconds (ms) | Standard Deviation 78 |
| NF1 Without Brain Tumor | Comparison of Relaxometry MRI Scans Between Low Grade Gliomas and Healthy Brain Tissue | T2 | 38 milliseconds (ms) | Standard Deviation 8 |
Comparison: Comparison of T1 valuesp-value: 0.0002Wilcoxon (Mann-Whitney)
Comparison: Comparison of T2 valuesp-value: 0.0003Wilcoxon (Mann-Whitney)
Secondary
Comparison of Scans of Treated and Untreated Low Grade Gliomas (LGG)
Using paired t-tests or non-parametric Wilcoxon signed rank tests, researchers will identify scans with significant differences in scans of treated and untreated tumors
Time frame: Up to 1 year
Population: Participants enrolled in study. Combination of Arms for reporting was pre-specified in the study protocol
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NF1-associated Optic Pathway Glioma (OPG) | Comparison of Scans of Treated and Untreated Low Grade Gliomas (LGG) | T2 | 57 milliseconds (ms) | Standard Deviation 15 |
| NF1-associated Optic Pathway Glioma (OPG) | Comparison of Scans of Treated and Untreated Low Grade Gliomas (LGG) | T1 | 1410 milliseconds (ms) | Standard Deviation 180 |
| NF1 Without Brain Tumor | Comparison of Scans of Treated and Untreated Low Grade Gliomas (LGG) | T1 | 1265 milliseconds (ms) | Standard Deviation 181 |
| NF1 Without Brain Tumor | Comparison of Scans of Treated and Untreated Low Grade Gliomas (LGG) | T2 | 47 milliseconds (ms) | Standard Deviation 15 |
Comparison: Comparison of T1 valuesp-value: 0.12Wilcoxon (Mann-Whitney)
Comparison: Comparison of T2 valuesp-value: 0.14Wilcoxon (Mann-Whitney)
Secondary
Number of Patients With Evaluable T1 and T2 Relaxation Times on MRF Scans
Number of patients which have evaluable scans at both T1 and T2
Time frame: Up to 1 year
Population: Participants enrolled in study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NF1-associated Optic Pathway Glioma (OPG) | Number of Patients With Evaluable T1 and T2 Relaxation Times on MRF Scans | 4 Participants |
| NF1 Without Brain Tumor | Number of Patients With Evaluable T1 and T2 Relaxation Times on MRF Scans | 6 Participants |
| Without NF1 and With Brain Tumor Exposed to Therapy | Number of Patients With Evaluable T1 and T2 Relaxation Times on MRF Scans | 6 Participants |
| Without NF1 and With Untreated Low Grade Brain Tumors | Number of Patients With Evaluable T1 and T2 Relaxation Times on MRF Scans | 8 Participants |
| Without NF1 and Without Brain Tumors | Number of Patients With Evaluable T1 and T2 Relaxation Times on MRF Scans | 4 Participants |
| Brain Tumors of Assorted Pathology | Number of Patients With Evaluable T1 and T2 Relaxation Times on MRF Scans | 6 Participants |
Other Pre-specified
Comparison of Relaxometry Values Between Tumors of Varying Pathology
Descriptive statistics will be used to identify the T1 and T2 relaxation times for tumors of different types on pre-operative MRF scan
Time frame: Up to 1 year