Sickle Cell Disease (SCD) impairs oxygen transport to tissue and causes endothelial injury. Thus, therapeutic interventions aim to improve both, but there is an unmet need for biomarkers to determine when intervention is necessary and evaluate the effectiveness of the chosen intervention in individual patients. This study proposes to monitor SCD and its treatment through their impact on cerebral hemodynamics, as the brain is one of the most vulnerable and consequential targets of the disease. Specifically, this study will optimize quantitative magnetic resonance imaging (MRI) and advanced optical spectroscopy techniques such as frequency-domain near-infrared and diffuse correlation spectroscopies (FDNIRS-DCS) to monitor 1) cerebral oxygen transport with measures of cerebral blood flow (CBF), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO2) and 2) endothelial function with cerebrovascular reactivity (CVR).
Additionally, this study aims to monitor baseline cerebral oxygen transport and CVR, as well as changes that occur with treatment (transfusion or genetic therapy to induce fetal hemoglobin) and assess hemoglobinopathy patients with known genotypes and phenotypes. The ultimate goal is to demonstrate the potential of this monitoring approach to select individual SCD subjects for interventions and evaluate individual responses to treatment. Success will help justify inclusion of these modalities in ongoing and future clinical trials of novel SCD therapies.
| Ellen Grant, MD | |
| 857-218-5111 | |
| [email protected] |
| Katherine Eident, BS | |
| 617-355-2184 | |
| [email protected] |
8 Years - 18 Years
Observational
All
Device
Group 1 (healthy controls):
Children ages 8-18 without SCD
Group 2 (SCD patients without treatment):
SCD patients ages 8-18 who:
have not undergone gene therapy or a bone marrow transplant
are not receiving chronic transfusions
have not received a blood transfusion in the past 3 months
Group 3 (SCD patients who have undergone gene therapy):
SCD patients ages 8-18 who have had gene therapy at least one month prior to enrollment
Group 4 (SCD patients who have chronic transfusions):
SCD patients ages 8-18 who receive chronic transfusions
Electrical implants such as cardiac pacemakers or perfusion pumps;
Ferromagnetic implants such as aneurysm clips, surgical clips, prosthesis, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants;
Ferromagnetic objects such as jewelry or metal clips;
Women of childbearing age who are seeking to become pregnant, who are breastfeeding, or who suspect they may be pregnant;
Pre-existing medical conditions including a likelihood of developing seizures or claustrophobic reactions;
Any greater than normal potential for cardiac arrest;
Subjects requiring sedation for MRI