Monitoring the haemodynamic response to visual stimulation in glaucoma patients

.SignificanceAdvances in electronics have allowed the recent development of compact, high channel count time domain functional near-infrared spectroscopy (TD-fNIRS) systems. Temporal moment analysis has been proposed for increased brain sensitivity due to the depth selectivity of higher order temporal moments. We propose a general linear model (GLM) incorporating TD moment data and auxiliary physiological measurements, such as short separation channels, to improve the recovery of the HRF.AimsWe compare the performance of previously reported multi-distance TD moment techniques to commonly used techniques for continuous wave (CW) fNIRS hemodynamic response function (HRF) recovery, namely block averaging and CW GLM. Additionally, we compare the multi-distance TD moment technique to TD moment GLM.ApproachWe augmented resting TD-fNIRS moment data (six subjects) with known synthetic HRFs. We then employed block averaging and GLM techniques with “short-separation regression” designed both for CW and TD to recover the HRFs. We calculated the root mean square error (RMSE) and the correlation of the recovered HRF to the ground truth. We compared the performance of equivalent CW and TD techniques with paired t-tests.ResultsWe found that, on average, TD moment HRF recovery improves correlations by 98% and 48% for HbO and HbR respectively, over CW GLM. The improvement on the correlation for TD GLM over TD moment is 12% (HbO) and 27% (HbR). RMSE decreases 56% and 52% (HbO and HbR) for TD moment compared to CW GLM. We found no statistically significant improvement in the RMSE for TD GLM compared to TD moment.ConclusionsProperly covariance-scaled TD moment techniques outperform their CW equivalents in both RMSE and correlation in the recovery of the synthetic HRFs. Furthermore, our proposed TD GLM based on moments outperforms regular TD moment analysis, while allowing the incorporation of auxiliary measurements of the confounding physiological signals from the scalp.

The hemodynamic response function (HRF) links neuronal activity to functional magnetic resonance imaging (fMRI) signals. While most fMRI studies use a canonical HRF, increasing evidence from studies of healthy subjects suggests that the HRF depends on anatomical location and disease states. Here, we investigate how HRF variability relates to anatomical location and pathology in the epileptic brain, using a large simultaneous electroencephalogram and fMRI dataset. Applying HRF deconvolution and temporal decomposition, we built the first whole-brain HRF library specific to epilepsy, identifying four distinct shape groups. We mapped HRF features across parcellations of two atlases using novel Bayesian hierarchical models. In non-epileptogenic regions, HRF shape and spatial distributions align with findings from healthy subjects. Within pathological regions, they vary significantly according to pathology. Our results indicate that HRF variability is associated with pathology, in addition to its dependence on anatomical location, motivating region- and pathology-based HRF modulation in epilepsy studies.

In an event-related functional MRI data analysis, an accurate and robust extraction of the hemodynamic response function (HRF) and its associated statistics (e.g., magnitude, width, and time to peak) is critical to infer quantitative information about the relative timing of the neuronal events in different brain regions. The aim of this paper is to develop a multiscale adaptive smoothing model (MASM) to accurately estimate HRFs pertaining to each stimulus sequence across all voxels. MASM explicitly accounts for both spatial and temporal smoothness information, while incorporating such information to adaptively estimate HRFs in the frequency domain. One simulation study and a real data set are used to demonstrate the methodology and examine its finite sample performance in HRF estimation, which confirms that MASM significantly outperforms the existing methods including the smooth finite impulse response model, the inverse logit model and the canonical HRF.

The purpose of this study is to characterize intraday and interday variation in central corneal thickness (CCT) in healthy and glaucomatous subjects. In this prospective cohort study, 40 healthy subjects and 42 subjects with primary open-angle glaucoma underwent CCT measurements by ultrasonic pachymetry on 5 days over 1 year: first at baseline, then at 1 week and 1, 6, and 12 months after baseline. On 1visit, CCT was measured every 2 hours from 08:00 to 20:00. Intraday CCT variance was compared with interday CCT variance. Mean CCT at all visits and time points ranged from 561 to 574 µm in healthy eyes and from 548 to 563 µm in glaucomatous eyes. The mean intraday CCT range (highest minus lowest readings) was 21±10 µm in healthy participants and 21±10 µm in glaucoma patients. The mean interday CCT range was 27±13 µm in healthy participants and 24±14 µm in glaucoma patients. Within-subject variance was significantly larger among the interday CCT measurements than the intraday CCT measurements in both healthy subjects and glaucoma patients (P<0.0001 for both) demonstrating that measurements taken on separate days are more different than measurements taken on the same day. Interday CCT differences of ≥30 µm were seen in 27.7% of normal subjects and 30% of glaucoma patients. CCT measurements exhibit intraday and interday variation, with the latter being significantly greater than the former. A single CCT assessment inadequately characterizes CCT and may impact risk assessment in patients with suspect and/or diagnosed glaucoma.

The oddball paradigm examines attentional processes by establishing neural substrates for target detection and novelty. Event-related functional imaging enables characterization of hemodynamic changes associated with these processes. We studied 36 healthy participants (17 men) applying a visual oddball event-related design at 4 Tesla, and performed an unbiased determination of the hemodynamic response function (HRF). Targets were associated with bilateral, albeit leftward predominant changes in frontal-parietal temporal and occipital cortices, and limbic and basal ganglia regions. Activation to novelty was more posteriorly distributed, and frontal activation occurred only on the right, while robust activation was seen in occipital regions bilaterally. Overlapping regions were left thalamus, caudate and cuneus and right parietal precuneus. While robust HRFs characterized most regions, target detection was associated with a negative HRF in the right parietal precuneus and a biphasic HRF in thalamus, basal ganglia, and all occipital regions. Both height of the HRF and longer time to peak in the right cingulate were associated with slower response time. Sex differences were observed, with higher HRF peaks for novelty in men in right occipital regions, and longer time to peak in the left hemisphere. Age was associated with reduced peak HRF in left frontal region. Thus, indices of the HRF can be used to better understand the relationship between hemodynamic changes and performance and can be sensitive to individual differences.

Department of Medicine Surgery, and Dentistry, University of Salerno, Salerno Italy Disclosure: The authors declare no conflict of interest.

.SignificanceDeaf and hard-of-hearing infants’ hemodynamic response function (HRF) has not yet been characterized. However, without an appropriate estimate of their HRF, neuroimaging modalities relying on hemodynamic responses, e.g., functional magnetic resonance imaging (fMRI) or functional near-infrared spectroscopy (fNIRS), cannot be used reliably in this population, e.g., prior to and following cochlear implantation. We contribute to better theoretical models of and more suitable therapeutic interventions for the neural changes induced by auditory and language deprivation in deaf infants.AimWe aim to characterize the parameters of the HRF of deaf and hard-of-hearing infants in response to Italian.ApproachWe measured 2- to 20-month-old Italian-exposed infants’ HRF to Italian using fNIRS in the bilateral temporal, i.e., auditory, cortices. We characterized the HRF for all infants and for three clinically relevant subsets: (i) monolingual Italian infants, (ii) genetically deaf infants, and (iii) infants aged 5 to 12 months. We computed the following parameters: peak amplitude, time-to-peak, full width at half maximum, and where present, the amplitude and latency of the initial dip and/or the final undershoot, using a model-based parameter fitting approach. We statistically compared these HRF parameters to those of typically hearing infants.ResultsDeaf and typically hearing infants showed largely similar HRFs, with both groups reaching comparable main peak amplitudes. Minor differences have been found in the latencies of some response components.ConclusionsOur results provide the first detailed characterization of the hemodynamic response to native-language speech in deaf and hard-of-hearing infants, improving clinical and therapeutic approaches through more accurate analysis of fMRI and fNIRS data.

The relation between electrophysiology and BOLD‐fMRI requires further elucidation. One approach for studying this relation is to find time‐frequency features from electrophysiology that explain the variance of BOLD time‐series. Convolution of these features with a canonical hemodynamic response function (HRF) is often required to model neurovascular coupling mechanisms and thus account for time shifts between electrophysiological and BOLD‐fMRI data. We propose a framework for extracting the spatial distribution of these time‐frequency features while also estimating more flexible, region‐specific HRFs. The core component of this method is the decomposition of a tensor containing impulse response functions using the Canonical Polyadic Decomposition. The outputs of this decomposition provide insight into the relation between electrophysiology and BOLD‐fMRI and can be used to construct estimates of BOLD time‐series. We demonstrated the performance of this method on simulated data while also examining the effects of simulated measurement noise and physiological confounds. Afterwards, we validated our method on publicly available task‐based and resting‐state EEG‐fMRI data. We adjusted our method to accommodate the multisubject nature of these datasets, enabling the investigation of inter‐subject variability with regards to EEG‐to‐BOLD neurovascular coupling mechanisms. We thus also demonstrate how EEG features for modelling the BOLD signal differ across subjects.

PurposeRecent studies have applied the new magnetic resonance encephalography (MREG) sequence to the study of interictal epileptic discharges (IEDs) in the electroencephalogram (EEG) of epileptic patients. However, there are no criteria to quantitatively evaluate different processing methods, to properly use the new sequence.MethodsWe evaluated different processing steps of this new sequence under the common generalized linear model (GLM) framework by assessing the reliability of results. A bootstrap sampling technique was first used to generate multiple replicated data sets; a GLM with different processing steps was then applied to obtain activation maps, and the reliability of these maps was assessed.ResultsWe applied our analysis in an event‐related GLM related to IEDs. A higher reliability was achieved by using a GLM with head motion confound regressor with 24 components rather than the usual 6, with an autoregressive model of order 5 and with a canonical hemodynamic response function (HRF) rather than variable latency or patient‐specific HRFs. Comparison of activation with IED field also favored the canonical HRF, consistent with the reliability analysis.ConclusionThe reliability analysis helps to optimize the processing methods for this fast fMRI sequence, in a context in which we do not know the ground truth of activation areas. Magn Reson Med 78:1–1, 2017. © 2016 International Society for Magnetic Resonance in Medicine

The hemodynamic response function (HRF) describes the dynamic process of the blood oxygen level dependent (BOLD) signal evoked by a very short stimulus of unit intensity. Understanding HRF is a key issue for exploring the underlying dynamics of nervous system activation. Some researches suggested that the shape of HRF varied with different brain regions and different subjects, even at different time point in the same brain region of a subject. In this work, epilepsy discharges were adopted as markers of short stimuli, and then we use EEG-fMRI method to investigate HRF in temporal lobe epilepsy with interictal regional slow wave. Five patients with idiopathic temporal lobe epilepsy were enrolled in this study, the peak delay and amplitude of the estimated HRF was compared with Gamma, Glover and the SPM canonical HRF, and the results show that the delay of the estimated HRF is different from either one of the three theoretical model, thus further study on both theoretical model and real data estimation is needed.

In the rodent brain the hemodynamic response to a brief external stimulus changes significantly during development. Analogous changes in human infants would complicate the determination and use of the hemodynamic response function (HRF) for functional magnetic resonance imaging (fMRI) in developing populations. We aimed to characterize HRF in human infants before and after the normal time of birth using rapid sampling of the Blood Oxygen Level Dependent (BOLD) signal. A somatosensory stimulus and an event related experimental design were used to collect data from 10 healthy adults, 15 sedated infants at term corrected post menstrual age (PMA) (median 41 + 1 weeks), and 10 preterm infants (median PMA 34 + 4 weeks). A positive amplitude HRF waveform was identified across all subject groups, with a systematic maturational trend in terms of decreasing time-to-peak and increasing positive peak amplitude associated with increasing age. Application of the age-appropriate HRF models to fMRI data significantly improved the precision of the fMRI analysis. These findings support the notion of a structured development in the brain's response to stimuli across the last trimester of gestation and beyond.

BackgroundThere is growing evidence for the idea of fMRI activation in white matter. In the current study, we compared hemodynamic response functions (HRF) in white matter and gray matter using 4 T fMRI. White matter fMRI activation was elicited in the isthmus of the corpus callosum at both the group and individual levels (using an established interhemispheric transfer task). Callosal HRFs were compared to HRFs from cingulate and parietal activation.ResultsExamination of the raw HRF revealed similar overall response characteristics. Finite impulse response modeling confirmed that the WM HRF characteristics were comparable to those of the GM HRF, but had significantly decreased peak response amplitudes.ConclusionsOverall, the results matched a priori expectations of smaller HRF responses in white matter due to the relative drop in cerebral blood flow (CBF) and cerebral blood volume (CBV). Importantly, the findings demonstrate that despite lower CBF and CBV, white matter fMRI activation remained within detectable ranges at 4 T.

OBJECTIVES: To evaluate retrobulbar hemodynamics in ophthalmic artery in primary open angle glaucoma and primary angle closure glaucoma compared with age and male matched controls. MATERIALS AND METHODS: Of the 1357 persons 35-64 years of age, who were examined in the MONICA in the Eye clinic of Kaunas Medical University Hospital from April 2001 till May 2002, glaucoma was 15 (30 eyes). All of them were performed CDI, visual field examination, gonioskopy. In this study we separate all glaucoma patients in Primary Open Angle Glaucoma (POAG) patients (N=11) group and Primary Angle Closure Glaucoma (PACG) patients (N=4) group. Only no operated eyes enrolled in POAG patient group (17 eyes) and all eyes enrolled in PACG patient group(8 eyes). In PACG patients group all patients were after various types of surgery and laser treatment. To asses the results of patients with POAG and PACG a control groups of healthy persons was formed. Dopplerography of ophthalmic artery was performed by means of the ultrasonic blood flow detector UDD – 03, developed on the bases of IBM PC 386 (Kaunas University of Technology), working in CDI mode for investigation of peripheral vessels. This instrument measures automatically Vmax during systole, blood flow velocity at the end of diastole V diast, PI (pulsatily index), RI (resistive index). The maximum measuring of depth – 35 mm, the frequency ultrasonic waves 8 MHz, intensivity of ultrasound 0,05). Pulsatily index PI in ophthalmic artery of glaucoma patients (POAG and PACG) was lower than in ophthalmic artery of healthy persons, but statistical not significant (p>0,05) too. We did not find differences in blood flow velocity at the end of diastole of the ophthalmic artery in glaucoma patients (POAG and PACG) and in control groups (p>0,05). CONCLUSIONS: 1. The peak systolic blood flow velocity in ophthalmic artery of POAG patients was statistical significant (p<0,05) lower than in ophthalmic artery of healthy persons. 2. The peak systolic blood flow velocity in ophthalmic artery was significantly lower in PACG patients compared to normal subjects. 3. Interpretation of CDI results must be careful

The aim of this study was to investigate the changes in vessel density (VD) in glaucoma patients and to investigate the relationship between VD and structural parameters using optical coherence tomography angiography. Our study included 25 primary open-angle glaucoma (POAG) patients, 25 pseudoexfoliation glaucoma (PXG) patients and 25 healthy individuals. All patients underwent 6 × 6mm retinal angiography (upper limit: internal limitan membrane [ILM], lower limit: 10µm inferior to inner plexiform layer) and 4.5 × 4.5mm disk angiography (upper limit: ILM, lower limit: posterior border of the retinal nerve fiber layer [RNFL]) via an optical coherence tomography (OCT) system (AngioVue, Optovue). Measures of vascular density were as follows: total area VD (tVD), intrapapillary VD (iVD), peripapillary VD (pVD) and parafoveal VD (pfVD). In addition to performing comparisons, the correlations between pVD, retinal nerve fiber layer (RNFL) thickness and optic nerve head measurement results were investigated. A total of 75 individuals were included in our study. In the POAG and PXG groups, tVD and pVD values were significantly lower than the control group (median tVDs were: 45.4, 45.9, 50.0, and median pVDs were: 50.0, 50.3, 53.1, respectively) (confidence intervals were: -9.8/-1.1 for pVD and -8.6/-1.4 for tVD). Significantly lower pf-VD values were detected in the PXG group compared to the control group (p < 0.05). There were strong positive correlations between RNFL thickness and pVD in in glaucoma groups (p < 0.001). There was no correlation between pVD and disk area, intraocular pressure and age in glaucoma patients. Patients using beta-blockers had significantly lower tVD and pVD values compared to those who did not (p < 0.05). The low VD values in glaucomatous eyes and the strong correlations between that values and RNFL thickness demonstrate a relationship between structural parameters and vascular parameters.

Reliability of the depth-dependent high-resolution BOLD hemodynamic response in human visual cortex and vicinity