Correlation results between regional mean ALFF and neurocognitive scores.

<p>Correlation results between regional mean ALFF and neurocognitive scores.</p

Cerebral volumes (expressed as mean ± standard deviation) of healthy controls (CTL), anemic control subjects (ACTL) and patients with sickle cell disease (SCD) and the p-values of SCD vs. CTL.

<p>Cerebral volumes (expressed as mean ± standard deviation) of healthy controls (CTL), anemic control subjects (ACTL) and patients with sickle cell disease (SCD) and the p-values of SCD vs. CTL.</p

Statistic results between the SCD patients with and without WMHs.

<p>Statistic results between the SCD patients with and without WMHs.</p

Representative one-sample <i>t</i>-test result of ALFF maps.

<p>(A) CTL subjects. (B) ACTL subjects. (C) SCD subjects. Color scale indicates t-values, resulting from one one sample t-test. Thresholds were set at a AlphaSim corrected p<0.05, determined by Monte Carlo simulation. In the Montreal Neurological Institute (MNI) template, the planes are X = -4mm, Z = -32mm and Y = -52mm for the sagittal, axial and coronal views, respectively.</p

Demographic and clinical variables among healthy controls (CTL), anemic control subjects (ACTL) and patients with sickle cell disease (SCD) including the transfused (NTx) and the non-transfused patients.

<p>Demographic and clinical variables among healthy controls (CTL), anemic control subjects (ACTL) and patients with sickle cell disease (SCD) including the transfused (NTx) and the non-transfused patients.</p

Differences in ALFF values between ACTL, SCD and CTL groups.

<p>All thresholds were set at a AlphaSim corrected p<0.05. Color scale indicates t-values, resulting from two sample t-test. Numbers and arrows represent anatomical location. Numbers and arrows represent anatomical location. A. Representative two-sample <i>t</i>-test results of ALFF maps between the ACTL versus CTL groups showing the right mSFG (arrow 1) and left insula (arrow 2). B. Representative two-sample <i>t</i>-test results of ALFF maps between the SCD versus CTL groups. Seven clusters are indicated by arrows: OFC (arrow 3), right paracentral lobule (arrow 4), PCC (arrow 5), cerebellum (arrow 6), frontal pole (arrow 7), left precuneus (arrow 8) and left insula (arrow 2). C. Representative two-sample <i>t</i>-test results of ALFF maps between the SCD versus ACTL groups. Compared with values in the ACTL group, ALFF in SCD patients increased in OFC (3) and decreased in right mSFG (arrow 1), cerebellum (arrow 6) and frontal pole (arrow 7).</p

Venn diagram representing changes (from normal) seen in SCD and ACTL groups.

<p>The changes are grouped with regards to their cause. They could be either unique to SCD patients (left/grey), common to SCD and ACTL patients (middle) or unique to ACTL patients (right/blue). OFC: orbital frontal cortex; ACC: anterior cingulate cortex; PCC: posterior cingulate cortex; mSFG: medial superior frontal gyrus.</p

Biophysical markers of the peripheral vasoconstriction response to pain in sickle cell disease

<div><p>Painful vaso-occlusive crisis (VOC), a complication of sickle cell disease (SCD), occurs when sickled red blood cells obstruct flow in the microvasculature. We postulated that exaggerated sympathetically mediated vasoconstriction, endothelial dysfunction and the synergistic interaction between these two factors act together to reduce microvascular flow, promoting regional vaso-occlusions, setting the stage for VOC. We previously found that SCD subjects had stronger vasoconstriction response to pulses of heat-induced pain compared to controls but the relative degrees to which autonomic dysregulation, peripheral vascular dysfunction and their interaction are present in SCD remain unknown. In the present study, we employed a mathematical model to decompose the total vasoconstriction response to pain into: 1) the neurogenic component, 2) the vascular response to blood pressure, 3) respiratory coupling and 4) neurogenic-vascular interaction. The model allowed us to quantify the contribution of each component to the total vasoconstriction response. The most salient features of the components were extracted to represent biophysical markers of autonomic and vascular impairment in SCD and controls. These markers provide a means of phenotyping severity of disease in sickle-cell anemia that is based more on underlying physiology than on genotype. The marker of the vascular component (BM_v) showed stronger contribution to vasoconstriction in SCD than controls (p = 0.0409), suggesting a dominant myogenic response in the SCD subjects as a consequence of endothelial dysfunction. The marker of neurogenic-vascular interaction (BM_n-v) revealed that the interaction reinforced vasoconstriction in SCD but produced vasodilatory response in controls (p = 0.0167). This marked difference in BM_n-v suggests that it is the most sensitive marker for quantifying combined alterations in autonomic and vascular function in SCD in response to heat-induced pain.</p></div

List of abbreviations.

<p>List of abbreviations.</p

Standardized FBV responses to a blood pressure pulse and derived biophysical marker BM_v.

<p>(a) <i>h</i>_<i>BPC</i>, standardized FBV responses to a blood pressure increase (mean ± SEM) of SCD (N = 22, thick line) and non-SCD (N = 23, thin line); (b) biophysical marker BM_v reflecting vasoconstriction as a result of blood pressure increase. Error bars show mean ± SEM. SCD had significantly stronger vasoconstriction than non-SCD after adjusting for age and sex (p = 0.0409).</p