Robert H. Small

Functional magnetic resonance imaging studies of pain: an investigation of signal decay during and across sessions.

Background:Several investigations into brain activation caused by pain have suggested that the multiple painful stimulations used in typical block designs may cause attenuation over time of the signal within activated areas. The effect this may have on pain investigations using multiple tasks has not been investigated. The signal decay across a task of four repeating pain stimulations and between two serial pain tasks separated by a 4-min interval was examined to determine whether signal attenuation may significantly confound pain investigations. Methods:The characteristics of the brain activation of six subjects were determined using whole brain blood oxygenation level–dependent functional magnetic resonance imaging on a 1.5-T scanner. Tasks included both tingling and pain induced by transcutaneous electrical stimulation of the median nerve. The average group maps were analyzed by general linear modeling with corrected cluster P values of less than 0.05. The time courses of individual voxels were further investigated by analysis of variance with P values of less than 0.05. Results:Significant differences between pain and tingling were found in the ipsilateral cerebellum, contralateral thalamus, secondary somatosensory cortex, primary somatosensory cortex, and anterior cingulate cortex. Highly significant signal decay was found to exist across each single pain task, but the signal was found to be restored after a 4-min rest period. Conclusions:This work shows that serial pain tasks can be used for functional magnetic resonance imaging studies using electrical nerve stimulation as a stimulus, as long as sufficient time is allowed between the two tasks.

Evaluation of a contact lens-embedded sensor for intraocular pressure measurement.

PurposeTo evaluate a novel contact lens-embedded pressure sensor for continuous measurement of intraocular pressure (IOP). MethodsRepeated measurements of IOP and ocular pulse amplitude (OPA) were recorded in 12 eyes of 12 subjects in sitting and supine positions using 3 configurations of the dynamic contour tonometer: slit-lamp mounted (DCT), hand-held (HH), and contact lens-embedded sensor (CL). The IOP and OPA for each condition were compared using repeated measures ANOVA and the 95% limits of agreement were calculated. ResultsThe sitting IOP (mean and 95% CI) for each configuration was DCT: 16.3 mm Hg (15.6 to 17.1 mm Hg), HH: 16.6 mm Hg (15.6 to 17.6 mm Hg), and CL: 15.7 mm Hg (15 to 16.3 mm Hg). The sitting OPA for each configuration was DCT: 2.4 mm Hg (2.1 to 2.6 mm Hg), HH: 2.4 mm Hg (2.1 to 2.7 mm Hg), and CL: 2.1 mm Hg (1.8 to 2.3 mm Hg). Supine IOP and OPA measurements with the CL and HH sensors were both greater than their corresponding sitting measurements, but were significantly less with the CL sensor than the HH sensor. The mean difference and 95% Limits of Agreement were smallest for the DCT and CL sensor comparisons (0.7±3.9 mm Hg) and widest for the CL and HH sensors (−1.9±7.25 mm Hg); these wider limits were attributed to greater HH measurement variability. ConclusionsThe CL sensor was comparable to HH and DCT sensors with sitting subjects and is a viable method for measuring IOP and OPA. Supine measurements of IOP and OPA were greater than sitting conditions and were comparatively lower with the CL sensor. HH measurements were more variable than CL measurements and this influenced the Limits of Agreement for both sitting and supine conditions.

The impact of physiologic noise correction applied to functional MRI of pain at 1.5 and 3.0 T

This study quantified the impact of the well-known physiologic noise correction algorithm RETROICOR applied to a pain functional magnetic resonance imaging (FMRI) experiment at two field strengths: 1.5 and 3.0 T. In the 1.5-T acquisition, there was an 8.2% decrease in time course variance (σ) and a 227% improvement in average model fit (increase in mean R(2)(a)). In the 3.0-T acquisition, significantly greater improvements were seen: a 10.4% decrease in σ and a 240% increase in mean R(2)(a). End-tidal carbon dioxide data were also collected during scanning and used to account for low-frequency changes in cerebral blood flow; however, the impact of this correction was trivial compared to applying RETROICOR. Comparison between two implementations of RETROICOR demonstrated that oversampled physiologic data can be applied by either downsampling or modification of the timing in the RETROICOR algorithm, with equivalent results. Furthermore, there was no significant effect from manually aligning the physiologic data with corresponding image slices from an interleaved acquisition, indicating that RETROICOR accounts for timing differences between physiologic changes and MR signal changes. These findings suggest that RETROICOR correction, as it is commonly implemented, should be included as part of the data analysis for pain FMRI studies performed at 1.5 and 3.0 T.

Comparison between end-tidal CO2 and respiration volume per time for detecting BOLD signal fluctuations during paced hyperventilation

Respiratory motion and capnometry monitoring were performed during blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) of the brain while a series of paced hyperventilation tasks were performed that caused significant hypocapnia. Respiration volume per time (RVT) and end-tidal carbon dioxide (ETCO(2)) were determined and compared for their ability to explain BOLD contrast changes in the data. A 35% decrease in ETCO(2) was observed along with corresponding changes in RVT. A best-fit ETCO(2) response function, with an average initial peak delay time of 12 s, was empirically determined. ETCO(2) data convolved with this response function was more strongly and prevalently correlated to BOLD signal changes than RVT data convolved with the corresponding respiration response function. The results suggest that ETCO(2) better models BOLD signal fluctuations in fMRI experiments with significant transient hypocapnia. This is due to hysteresis in the ETCO(2) response when moving from hypocapnia to normocapnia, compared to moving from normocapnia to hypocapnia.

Characteristics of the cerebrospinal fluid pressure waveform and craniospinal compliance in idiopathic intracranial hypertension subjects

BackgroundIdiopathic intracranial hypertension (IIH) is a condition of abnormally high intracranial pressure with an unknown etiology. The objective of this study is to characterize craniospinal compliance and measure the cerebrospinal fluid (CSF) pressure waveform as CSF is passively drained during a diagnostic and therapeutic lumbar puncture (LP) in IIH.MethodsEighteen subjects who met the Modified Dandy Criteria, including papilledema and visual field loss, received an ultrasound guided LP where CSF pressure (CSFP) was recorded at each increment of CSF removal. Joinpoint regression models were used to calculate compliance from CSF pressure and the corresponding volume removed at each increment for each subject. Twelve subjects had their CSFP waveform recorded with an electronic transducer. Body mass index, mean CSFP, and cerebral perfusion pressure (CPP) were also calculated. T-tests were used to compare measurements, and correlations were performed between parameters.ResultsCerebrospinal fluid pressure, CSFP pulse amplitude (CPA), and CPP were found to be significantly different (p < 0.05) before and after the LP. CSFP and CPA decreased after the LP, while CPP increased. The craniospinal compliance significantly increased (p < 0.05) post-LP. CPA and CSFP were significantly positively correlated.ConclusionsBoth low craniospinal compliance (at high CSFP) and high craniospinal compliance (at low CSFP) regions were determined. The CSFP waveform morphology in IIH was characterized and CPA was found to be positively correlated to the magnitude of CSFP. Future studies will investigate how craniospinal compliance may correlate to symptoms and/or response to therapy in IIH subjects.

Ocular pressure waveform reflects ventricular bigeminy and aortic insufficiency.

Ocular pulse amplitude (OPA) is defined as the difference between maximum and minimum intraocular pressure (IOP) during a cardiac cycle. Average values of OPA range from 1 to 4 mmHg. The purpose of this investigation is to determine the source of an irregular IOP waveform with elevated OPA in a 48-year-old male. Ocular pressure waveforms had an unusual shape consistent with early ventricular contraction. With a normal IOP, OPA was 9 mmHg, which is extraordinarily high. The subject was examined by a cardiologist and was determined to be in ventricular bigeminy. In addition, he had bounding carotid pulses and echocardiogram confirmed aortic insufficiency. After replacement of the aortic valve, the bigeminy resolved and the ocular pulse waveform became regular in appearance with an OPA of 1.6–2.0 mmHg. The ocular pressure waveform is a direct reflection of hemodynamics. Evaluating this waveform may provide an additional opportunity for screening subjects for cardiovascular anomalies and arrhythmias.