Ultrasound velocity in human muscle in vivo: perspective for edema studies

The present study examines the association of the changes in ultrasound velocity measured at 1 MHz using 1.5 micros duration tone burst in the human soleus muscle in vivo with several pathologies including patients with chronic renal failure (CRF) and disorders of the cardiovascular system. Total 127 subjects were investigated, with approximately equal number of male and female subjects uniformly distributed by age, from 15 to 70 years old. Since molecular composition of the tissue is thought to have greater effect on the bulk ultrasound velocity, potential contribution of both water and fat, two main variable components of a muscle, were taken into account. Observed negative correlation of ultrasound velocity with the body mass index was considered a result of an elevated fat content. Based on the obtained data, presence of leg edemas results in a measurably lower ultrasound velocity in the soleus muscle. Unless patients had visibly detected leg edema, no difference between healthy individuals, patients with chronic heart failure, or CRF was found. Despite relatively high individual variations in velocity, ranging from 1530 to 1615 m/s, a statistically significant gender correlated difference between average values of the velocity was observed. No dependence of velocity on subject age was detected. An indirect confirmation of the muscle fluid homeostasis was revealed in patients with CRF undergoing hemodialysis procedure. After hemodialysis, a significantly smaller increase (0.3% in average) of ultrasound velocity in the soleus muscle was observed than otherwise could be expected if a uniform relative loss of total body fluids was assumed (1-1.3%). In general, the study findings set a premise for using ultrasound velocity as a potential quantitative parameter for edema assessment.     

Ethylene and ammonia traces measurements from the patients’ breath with renal failure via LPAS method

The application of laser photoacoustic spectroscopy (LPAS) for fast and precise measurements of breath biomarkers has opened up new promises for monitoring and diagnostics in recent years, especially because breath test is a non-invasive method, safe, rapid and acceptable to patients. Our study involved assessment of breath ethylene and breath ammonia levels in patients with renal failure receiving haemodialysis (HD) treatment. Breath samples from healthy subjects and from patients with renal failure were collected using chemically inert aluminized bags and were subsequently analyzed using the LPAS technique. We have found out that the composition of exhaled breath in patients with renal failure contains not only ethylene, but also ammonia and gives valuable information for determining efficacy and endpoint of HD.     

Proton magnetic resonance spectroscopy of the kidney in renal stone disease

Previous studies of renal stone disease (RSD) in Thailand indicated abnormal urinary aggregator and inhibitor composition among farmers with excessive sweat loss. Our aim was to compare the proton MR spectra obtained from the kidneys of 32 proven cases of RSD (aged 38 to 65 yrs) with nine age-matched normal control subjects. We used the STEAM sequence with TE = 15 ms and TR = 2000 ms. The spectra at 3.25, 3.6 and 3.9 ppm were analyzed. The results showed a correlation between the three peaks (p < 0.001), however, there was no significant difference between the RSD group and the normal control subjects. We therefore concluded that there was no overloading of these osmolytes among the renal stone patients.     

Initial changes of non-traumatic osteonecrosis of femoral head in fat suppression images: bone marrow edema was not found before the appearance of band patterns

The present study examined initial changes in non-traumatic osteonecrosis of the femoral head (ONF) on T1- and T2-weighted MR images, and fat suppression images. The subjects were 57 renal transplant recipients (37 males and 20 females), whose median age at the time of transplantation was 31.5 years old (range, 10 to 58 years). Twelve patients developed band patterns (sign of established ONF) at an early postoperative period. Among them, 4 joints of 3 patients had a localized, faint signal abnormality in fat suppression images, where band pattern was confirmed later in T1- and T2-weighted images. In all the 57 patients, no bone marrow edema preceding to ONF was observed. Bone marrow edema would not be the cause of ONF in renal transplant patients. Early changes depicted in our fat suppression images would be useful information in the studies on pathogenesis of ONF.     

Functional magnetic resonance imaging of human renal allografts during the post-transplant period: Preliminary observations

Graft dysfunction is a common occurrence during the first weeks following renal transplantation. The current study was designed to evaluate the potential of renal magnetic resonance (MR) perfusion imaging to differentiate acute allograft rejection (AAR) from acute tubular necrosis (ATN) during the post-transplant period. Twenty-three consecutive patients with clinically suspected ATN and/or AAR and eight consecutive control patients (asymptomatic, serum creatinine concentration < 1.5 mg/dL) underwent MR perfusion imaging of the renal allograft within 64 days after transplantation. Histopathology was obtained in all cases with clinical suspicion of ATN or AAR. Sixty sequential fast gradient-recalled-echo MR images were acquired in each patient after intravenous administration of gadolinium-DTPA (0.1 mmol/kg). Histopathology revealed 6 patients with pure AAR, 4 patients with a combination of AAR and ATN, 12 patients with ATN and 1 patient with normal findings. Kidney graft recipients with normal renal function showed a moderate increase in signal intensity (SI) of the renal cortex and medulla after administration of contrast agent followed by an immediate and short decrease in SI of the medulla (biphasic medullary enhancement pattern). The increase in cortical SI of patients with AAR was significantly smaller (61 ± 4% increase above baseline) than that measured in normal allografts (136 ± 9% increase above baseline) (p < 0.05) and patients with ATN (129 ± 3% increase above baseline) (p < .05). Patients with ATN had a slightly delayed and diminished cortical enhancement and an uniphasic and lesser medullary enhancement pattern compared to that observed in normal allografts (p < 0.05). A close correlation (r = 0.72) was found between serum creatinine concentration levels and changes in SI. Thus, MR imaging results and histopathology were in agreement in 22 of 23 patients (96%). MR perfusion imaging of renal allografts can be used to noninvasively differentiate ATN from AAR during the post-transplant period, and may also be helpful in cases where covert AAR is superimposing ATN during a phase of anuria. Patients with ATN can be separated from normals in the majority of cases as reflected by an uniphasic medullary enhancement pattern.     

Noise and sleep at home,a field study on primary and after-effects

The sleep of 20 healthy subjects (10 male, 10 female, 25–63 years) who lived more than one year in streets with high traffic load were recorded during 12 consecutive nights each. Throughout every night EEG, EOG, and sound pressure levels were recorded. In the morning and in the evening as well the subjects completed a short questionnaire and executed a reaction time test. During the experimental phase (five nights) noise level was attenuated by earplugs in 10 subjects, and the other 10 subjects who usually slept with closed windows slept with open windows. Compared to the control nights the 1%-noise level changed by 9 dB(A). In comparison with other variables (age, sex, personality) noise influenced the course of sleep slightly. Small negative effects were found for some physiological, for subjective, and for performance data indicating that there is no (complete) habituation to the usual acoustical environment.     

Optimization of scantiming in abdominal breathhold contrast-enhanced MRA: an empirical guideline

The objective of this study to determine a suitable scan timing scheme in contrast enhanced MRA for the depiction of the arterial, the portal and the systemic venous system in the abdomen with maximum signal intensity in healthy subjects and in patients with cirrhosis. The signal intensity in the aorta, hepatic artery, portal vein, left renal vein and the supra- and infrarenal IVC were measured in 40 consecutive orthotopic liver transplantation candidates with cirrhosis and 20 healthy renal donors in a bolus triggered arterial scan and after 30, 60, 90 and 150 s respectively. The aorta and hepatic artery showed the highest signal intensity on the arterial scan. The portal and left renal vein showed the highest signal intensity after 30 s, the suprarenal IVC after 60 s and the infrarenal IVC after 90 s. No significant differences were found between healthy subjects and patients with cirrhosis. The arterial, portal and systemic venous system in the abdomen can be visualized selectively with maximum signal intensity by proper timing of the scans, hereby reducing redundant scans. Scanning at just the right time to achieve optimal vessel opacification can be promoted by using data from this study. The proposed scan scheme is suitable for subjects with and without cirrhosis.     

An integrated approach based on uniform quantization for the evaluation of complexity of short-term heart period variability: Application to 24 h Holter recordings in healthy and heart failure humans

We propose an integrated approach based on uniform quantization over a small number of levels for the evaluation and characterization of complexity of a process. This approach integrates information-domain analysis based on entropy rate, local nonlinear prediction, and pattern classification based on symbolic analysis. Normalized and non-normalized indexes quantifying complexity over short data sequences ( approximately 300 samples) are derived. This approach provides a rule for deciding the optimal length of the patterns that may be worth considering and some suggestions about possible strategies to group patterns into a smaller number of families. The approach is applied to 24 h Holter recordings of heart period variability derived from 12 normal (NO) subjects and 13 heart failure (HF) patients. We found that: (i) in NO subjects the normalized indexes suggest a larger complexity during the nighttime than during the daytime; (ii) this difference may be lost if non-normalized indexes are utilized; (iii) the circadian pattern in the normalized indexes is lost in HF patients; (iv) in HF patients the loss of the day-night variation in the normalized indexes is related to a tendency of complexity to increase during the daytime and to decrease during the nighttime; (v) the most likely length L of the most informative patterns ranges from 2 to 4; (vi) in NO subjects classification of patterns with L=3 indicates that stable patterns (i.e., those with no variations) are more present during the daytime, while highly variable patterns (i.e., those with two unlike variations) are more frequent during the nighttime; (vii) during the daytime in HF patients, the percentage of highly variable patterns increases with respect to NO subjects, while during the nighttime, the percentage of patterns with one or two like variations decreases.     

Short echo time in vivo prostate ¹H-MRSI

Visualization of short echo time (TE) metabolites in prostate magnetic resonance spectroscopic imaging is difficult due to lipid contamination and pulse timing constraints. In this work, we present a modified pulse sequence to permit short echo time (TE=40ms) acquisitions with reduced lipid contamination for the detection of short TE metabolites. The modified pulse sequence employs the conformal voxel MRS (CV-MRS) technique, which automatically optimizes the placement of spatial saturation planes to adapt the excitation volume to the shape of the prostate, thus reducing lipid contamination in prostate magnetic resonance spectroscopic imaging (MRSI). Metabolites were measured and assessed using a modified version of LCModel for analysis of in vivo prostate spectra. We demonstrate the feasibility of acquiring high quality spectra at short TEs, and show the measurement of short TE metabolites, myo-inositol, scyllo-inositol, taurine and glutamine/glutamate for both single and multi-voxel acquisitions. In single voxels experiments, the reduction in TE resulted in 57% improvement in the signal-to-noise ratio (SNR). Additional 3D MRSI experiments comparing short (TE=40 ms), and long (TE=130 ms) TE acquisitions revealed a 35% improvement in the number of adequately fitted metabolite peaks (775 voxels over all subjects). This resulted in a 42 ± 24% relative improvement in the number of voxels with detectable citrate that were well-fitted using LCmodel. In this study, we demonstrate that high quality prostate spectra can be obtained by reducing the TE to 40 ms to detect short T2 metabolites, while maintaining positive signal intensity of the spin-coupled citrate multiplet and managing lipid suppression.     

The effect of competing melodies on melody recognition by hearing-impaired and normal-hearing listeners

For a group of 30 hearing-impaired subjects and a matched group of 15 normal-hearing subjects (age range 13-17) the following data were collected: the tone audiogram, the auditory bandwidth at 1000 Hz, and the recognition threshold of a short melody presented simultaneously with two other melodies, lower and higher in frequency, respectively. The threshold was defined as the frequency distance required to recognize the test melody. It was found that, whereas the mean recognition threshold for the normal-hearing subjects was five semitones, it was, on the average, 27 semitones for the hearing-impaired subjects. Although the interindividual spread for the latter group was large, it did not correlate with the subjects' auditory bandwidth, nor with their musical experience or education.     

Evaluating renal arterial wall by non-enhanced 2D and 3D free-breathing black-blood techniques: Initial experience

ObjectivesTo evaluate the feasibility and reproducibility of 2D and 3D black-blood sequences in measuring morphology of renal arterial wall.MethodsThe 2D and 3D imaging sequences used variable-refocusing-flip-angle and constant-low-refocusing-flip-angle turbo spin echo (TSE) readout respectively, with delicately selected black-blood scheme and respiratory motion trigger for free-breathing imaging. Fourteen healthy subjects and three patients with Takayasu arteritis underwent renal artery wall imaging with 3D double inversion recovery (DIR) TSE and 2D Variable Flip Angle-TSE (VFA-TSE) black-blood sequences at 3.0 T. Four healthy subjects were randomly selected for scan-rescan reproducibility experiments. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and morphology of arterial wall were measured and compared using paired-t-test or Wilcoxon signed-rank test between 2D and 3D sequences. The inter-observer, intra-observer and scan-rescan agreements of above measurements were determined using intraclass correlation coefficient (ICC).ResultsThe 2D and 3D imaging sequences showed similar morphological measurements (lumen area, wall area, mean wall thickness and maximum wall thickness) of renal arterial wall (all P > 0.05) and excellent agreement (ICC: 0.853–0.954). Compared to 2D imaging, 3D imaging exhibited significantly lower SNR_lumen (P < 0.01) and SNR_wall (P = 0.037), similar contrast-to-noise ratio (CNR) (P = 0.285), and higher CNR efficiency (CNR_eff) (P < 0.01). Both 2D and 3D imaging showed good to excellent inter-observer (ICC: 0.723–0.997), intra-observer (ICC: 0.749–0.996) and scan-rescan (ICC: 0.710–0.992) reproducibility in measuring renal arterial wall morphology, SNR and CNR, respectively.ConclusionsBoth high-resolution free-breathing 2D VFA-TSE and 3D DIR TSE black-blood sequences are feasible and reproducible in high-resolution renal arterial wall imaging. The 2D imaging has high SNR, whereas 3D imaging has high imaging efficiency.     

A preliminary study of blood-oxygen-level-dependent MRI in patients with chronic kidney disease

Background

Blood-oxygen-level-dependent (BOLD) magnetic resonance imaging (MRI) can provide regional measurements of oxygen content using deoxyhemoglobin paramagnetic characteristics. The apparent relaxation rate or R2*(=1/T2*) can be determined from the slope of log (intensity) versus echo time and is directly proportional to the tissue content of deoxyhemoglobin. Thus, as the level of deoxyhemoglobin increases, T2* will decrease, leading to an increase in R2*. Chronic kidney disease (CKD) can affect oxygenation levels in renal parenchyma, which influences the clinical course of the disease. The goal of this study was to detect and assess renal oxygenation levels in CKD using BOLD MRI.

Methods

Fifteen healthy subjects and 11 patients with CKD underwent a renal scan using multigradient-recalled-echo sequence with eight echoes. R2* (1/s) of the renal cortex and medulla was measured on BOLD images. Of the 11 patients, nine had biopsy-proven chronic glomerulonephritis, and two had a similar diagnosis based on clinical symptoms and investigations.

Results

Mean medullary R2* (MR2*) and cortex R2* (CR2*) levels were significantly higher in patients (22 kidneys, MR2*=24.79±4.84 s⁻¹, CR2*=18.97±2.72 s⁻¹) than in controls (30 kidneys, MR2*=19.98±1.19 s⁻¹, CR2*=16.03±1.23 s⁻¹) (P<.01), and MR2* was increased more than CR2*. Medullary to cortical R2* ratios (MCR2*) of patients were significantly increased when compared with those of controls (P<.01). In the patient group, estimated glomerular filtration rate levels were greater than or equal to 60 ml/min/1.73 m² in six patients (12 kidneys), whose MR2* and CR2* were also significantly higher than those of controls (P<.01). Serum creatinine levels were normal in seven patients (14 kidneys), whose MR2*, CR2* and MCR2* were also higher than those of controls (P<.01).

Conclusions

BOLD MRI can be used to evaluate changes in renal oxygenation in CKD, suggesting that it has the potential to be an excellent noninvasive tool for the evaluation of renal function.     

10.5 T MRI static field effects on human cognitive,vestibular, and physiological function

PurposeTo perform a pilot study to quantitatively assess cognitive, vestibular, and physiological function during and after exposure to a magnetic resonance imaging (MRI) system with a static field strength of 10.5 Tesla at multiple time scales.MethodsA total of 29 subjects were exposed to a 10.5 T MRI field and underwent vestibular, cognitive, and physiological testing before, during, and after exposure; for 26 subjects, testing and exposure were repeated within 2–4 weeks of the first visit. Subjects also reported sensory perceptions after each exposure. Comparisons were made between short and long term time points in the study with respect to the parameters measured in the study; short term comparison included pre-vs-isocenter and pre-vs-post (1–24 h), while long term compared pre-exposures 2–4 weeks apart.ResultsOf the 79 comparisons, 73 parameters were unchanged or had small improvements after magnet exposure. The exceptions to this included lower scores on short term (i.e. same day) executive function testing, greater isocenter spontaneous eye movement during visit 1 (relative to pre-exposure), increased number of abnormalities on videonystagmography visit 2 versus visit 1 and a mix of small increases (short term visit 2) and decreases (short term visit 1) in blood pressure. In addition, more subjects reported metallic taste at 10.5 T in comparison to similar data obtained in previous studies at 7 T and 9.4 T.ConclusionInitial results of 10.5 T static field exposure indicate that 1) cognitive performance is not compromised at isocenter, 2) subjects experience increased eye movement at isocenter, and 3) subjects experience small changes in vital signs but no field-induced increase in blood pressure. While small but significant differences were found in some comparisons, none were identified as compromising subject safety. A modified testing protocol informed by these results was devised with the goal of permitting increased enrollment while providing continued monitoring to evaluate field effects.     

Magnetic resonance imaging of cortical bone with ultrashort TE pulse sequences

PurposeNormal adult cortical bone has a very short T₂ and characteristically produces no signal with pulse sequence echo times (TEs) routinely used in clinical practice. We wished to determine whether it was possible to use ultrashort TE (UTE) pulse sequences to detect signal from cortical bone in human subjects and use this signal to characterise this tissue.Subjects and MethodsSeven volunteers and 10 patients were examined using ultrashort TE pulse sequences (TE=0.07 or 0.08 ms). Short and long inversion as well as fat suppression pulses were used as preparation pulses. Later echo images were also obtained as well as difference images produced by subtracting a later echo image from a first echo image. Saturation pulses were used for T₁ measurement and sequences with progressively increasing TEs for T₂* measurement. Intravenous gadodiamide was administered to four subjects.ResultsSignal in cortical bone was detected with UTE sequences in children, normal adults and patients. This signal was usually made more obvious by subtracting a later echo image from the first provided that the signal-to-noise ratio was sufficiently high.Normal mean adult T₁s ranged from 140 to 260 ms, and mean T₂*s ranged from 0.42 to 0.50 ms. T₁ increased significantly with age (P<.01).Increased signal was observed after contrast enhancement in the normal volunteer and the three patients to whom it was administered.Reduction in signal from short T₂ components was seen in acute fractures, and increase in signal in these components was seen with new bone formation after fracture malunion. In a case of osteoporosis, bone cross-sectional area and signal level appeared reduced.ConclusionSignal can be detected from normal and abnormal cortical bone with UTE pulse sequences, and this can be used to measure its T₁ and T₂* as well as observe contrast enhancement. Difference images are of value in increasing the conspicuity of cortical bone and observing abnormalities in disease.     

Effects of Cardiac Resynchronization Therapy on Cardio-Respiratory Coupling

In this study, the effect of cardiac resynchronization therapy (CRT) on the relationship between the cardiovascular and respiratory systems in heart failure subjects was examined for the first time. We hypothesized that alterations in cardio-respiratory interactions, after CRT implantation, quantified by signal complexity, could be a marker of a favorable CRT response. Sample entropy and scaling exponents were calculated from synchronously recorded cardiac and respiratory signals 20 min in duration, collected in 47 heart failure patients at rest, before and 9 months after CRT implantation. Further, cross-sample entropy between these signals was calculated. After CRT, all patients had lower heart rate and CRT responders had reduced breathing frequency. Results revealed that higher cardiac rhythm complexity in CRT non-responders was associated with weak correlations of cardiac rhythm at baseline measurement over long scales and over short scales at follow-up recording. Unlike CRT responders, in non-responders, a significant difference in respiratory rhythm complexity between measurements could be consequence of divergent changes in correlation properties of the respiratory signal over short and long scales. Asynchrony between cardiac and respiratory rhythm increased significantly in CRT non-responders during follow-up. Quantification of complexity and synchrony between cardiac and respiratory signals shows significant associations between CRT success and stability of cardio-respiratory coupling.     

Improved MR imaging for patients with metallic implants

Pediatric oncology patients with large metallic prostheses were imaged with one of two MR imaging techniques: 1) the "tilted view-angle" technique, 2) or a higher readout bandwidth technique. The tilted view-angle method uses an additional gradient in the slice selection direction during readout. The high bandwidth technique increases the readout bandwidth and shortens the echo time (TE). High bandwidth and short echo times were implemented in both T(1)-weighted (T(1)W) turbo spin echo and turbo short tau inversion recovery (STIR) sequences. Both imaging techniques reduced the size of metal-induced image artifacts. The tilted view-angle method reduced the artifact to a greater degree but had inherent shortcomings. The reformatted images were blurred and shifted. The area of interest was often moved outside of the field of view, unless parameters were adjusted on the basis of a pre-scan calculation. The high readout bandwidth, short echo technique required no special preparation and reduced metal artifacts without image blurring. The combination of high-bandwidth, shorter echo turbo STIR and T(1)W turbo spin echo sequences with subtraction of pre- from post-contrast images allowed effective fat suppression without local field inhomogeneity affects. This greatly improved our ability to evaluate suspected disease near metallic implants in pediatric cancer patients.     

Neck and Shoulder Muscle Activity and Thorax Movement in Singing and Speaking Tasks with Variation in Vocal Loudness and Pitch

The aim of this study was to examine respiratory phasing and loading levels of sternocleidomastoideus (STM), scalenus (SC), and upper trapezius (TR) muscles in vocalization tasks with variation in vocal loudness and pitch. Eight advanced singing students, aged 22 to 28 years, participated. Surface electromyographic (EMG) activity was recorded from STM, SC, and TR. Thorax movement was detected by two strain gauge sensors placed around the upper (upper TX) and lower (lower TX) thorax. A glissando and simplified singing and speaking tasks were performed. Sustained vowels /a:-i-ae-o:/ were sung in a glissando from lowest to highest pitch (mixed voice/falsetto) back to lowest pitch and in short singing sequences at comfortable, low, and high pitches. The same vowels were spoken softly and loudly for about the same length. The subjects inhaled between the vowels. It was concluded that the inspiratory phased STM and SC muscles produced a counterforce to compression of upper TX at high pitches in glissando. STM and SC were activated to higher levels during phonation than in inhalation. As breathing demands were reduced, STM and SC activity was lowered and the respiratory phasing of peak amplitude changed to inhalation. TR contributed to exhalation in demanding singing with long breathing cycles, but it was less active in singing tasks with short breathing cycles and was essentially inactive in simplified speaking tasks.     

Evaluation of the prostate by magnetic resonance imaging

Forty-seven male patients with suspected prostatic disease underwent magnetic resonance imaging (MRI) of the pelvis on a Picker resistive magnet operating at 0.15 T; 33 had histologically proved adenocarcinoma, 12 benign prostatic hypertrophy, 1 a transitional cell carcinoma, and 1 a seminoma. Eleven normal subjects also were included in the study. The study attempted to (1) define the MRI characteristics of the normal prostate, benign prostatic hypertrophy, and prostatic adenocarcinoma, (2) evaluate various pulse sequences in imaging the prostate, and (3) compare MRI findings with clinical, pathologic, and computed tomography results. Various pulse sequences, including inversion recovery and spin-echo with short and long TE and TR, were used. MRI was sensitive in detecting intracapsular and extracapsular prostatic disease. The finding of inhomogeneous signal texture throughout the gland was a sensitive but nonspecific finding for adenocarcinoma. A focal nodule with prolonged T1 and T2 relaxation times was the most specific MRI finding for adenocarcinoma. Extracapsular spread of neoplasm was often demonstrated, and because of its superior soft-tissue contrast ability, MRI was more accurate than computed tomography in delineating extracapsular extension.     

An acoustic model of a multiple-channel cochlear implant

A set of bandpass filtered, pulsed noise stimuli presented to three normally hearing subjects was found to have psychophysical properties similar to those of a set of pulsed electrical stimuli presented to two cochlear implant patients. Identical procedures were used to compare the performances of the two groups of subjects in the following tasks: (a) pulse rate difference limen measurements, (b) pitch scaling for stimuli differing in pulse rate, (c) pitch scaling and categorization of stimuli differing in filter frequency or electrode position, and (d) similarity judgments of stimuli differing in pulse rate and filter frequency or electrode position. By choosing the parameters of the acoustic stimuli appropriately, a high level of agreement between the two sets of results was achieved. Electrical stimuli on electrodes at different sites in the cochlea were matched with pulsed noise passed through bandpass filters with different center frequencies. Matching was achieved for equal electrical and acoustic pulse rates.     

Dynamics and nonlinearities of the BOLD response at very short stimulus durations

In designing a functional imaging experiment or analyzing data, it is typically assumed that task duration and hemodynamic response are linearly related to each other. However, numerous human and animal studies have previously reported a deviation from linearity for short stimulus durations (<4 s). Here, we investigated nonlinearities of blood-oxygenation-level-dependent (BOLD) signals following visual stimulation of 5 to 1000 ms duration at two different luminance levels in human subjects. It was found that (a) a BOLD response to stimulus durations as short as 5 ms can be reliably detected; this stimulus duration is shorter than employed in any previous study investigating BOLD signal time courses; (b) the responses are more nonlinear than in any other previous study: the BOLD response to 1000 ms stimulation is only twice as large as the BOLD response to 5 ms stimulation although 200 times more photons were projected onto the retina; (c) the degree of nonlinearity depends on stimulus intensity; that is, nonlinearities have to be characterized not only by stimulus duration but also by stimulus features like luminance. These findings are especially of most practical importance in rapid event-related functional magnetic resonance imaging (fMRI) experimental designs. In addition, an 'initial dip' response--thought to be generated by a rapid increase in cerebral metabolic rate of oxygen metabolism (CMRO2) relative to cerebral blood flow--was observed and shown to colocalize well with the positive BOLD response. Highly intense stimulation, better tolerated by human subjects for short stimulus durations, causes early CMRO2 increase, and thus, the experimental design utilized in this study is better for detecting the initial dip than standard fMRI designs. These results and those from other groups suggest that short stimulation combined with appropriate experimental designs allows neuronal events and interactions to be examined by BOLD signal analysis, despite its slow evolution.