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Biomedical subjects

Deniz Bilecen

Publications and source records attributed to Deniz Bilecen.

At least 19 recordsLinked to original sources

Calf muscles imaged at BOLD MR: correlation with TcPO2 and flowmetry measurements during ischemia and reactive hyperemia--initial experience.

PURPOSE: To prospectively compare the blood oxygen level-dependent (BOLD) magnetic resonance (MR) signal intensity of calf muscle during ischemia and reactive hyperemia with laser Doppler flowmetry (LDF) and transcutaneous oxygen pressure (TcPo2) measurements, two parameters routinely used to evaluate peripheral arterial occlusive disease. MATERIALS AND METHODS: The study was institutional review board approved; all volunteers gave informed consent. Fifteen healthy volunteers (eight male, seven female; mean age, 33.0 years +/- 6.1 [standard deviation]) underwent LDF, TcPo2 measurement, and BOLD MR imaging of the calf during ischemia and reactive hyperemia. The BOLD signal intensity of the gastrocnemius muscle was measured at 1.5-T single-shot multiecho gradient-echo echo-planar imaging. Time to half ischemia minimum (THIM), time to half hyperemia peak (THHP), and time to peak (TTP) after cuff deflation were measured with each method. Correlation coefficients (CCs) for associations of BOLD response with LDF and TcPo2 time courses were calculated. Student t testing of key BOLD MR, LDF, and TcPo2 measurement parameters was performed. RESULTS: During ischemia, normalized LDF and TcPo2 measurements decreased similarly to BOLD MR signal intensity (CCs: 0.86 and 0.96 for associations with LDF and TcPo2 measurements, respectively). Mean THIM values were 136.0, 82.5, and 121.3 seconds for BOLD MR, LDF (P < .01), and TcPo2 (P > .05) measurements, respectively. During early reactive hyperemia, LDF and TcPo2 measurements increased rapidly to peak values, similarly to BOLD MR signal intensity (CCs: 0.81 and 0.78, respectively). Mean THHP values were 26.0, 12.5, and 44.0 seconds for BOLD MR, LDF (P < .01), and TcPo2 (P < .01) measurements, respectively. Mean TTP values were 48.7, 47.5, and 98.0 seconds for BOLD MR, LDF (P > .05), and TcPo2 (P < .01) measurements, respectively. CONCLUSION: BOLD MR imaging of calf muscles-depending on underlying key parameters-has moderate to good correlation with LDF and TcPo2 measurements during ischemia and reactive hyperemia.

Adult↗

Blood oxygenation level-dependent magnetic resonance imaging of the skeletal muscle in patients with peripheral arterial occlusive disease.

BACKGROUND: Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) has been used to measure T2* changes in skeletal muscle tissue of healthy volunteers. The BOLD effect is assumed to primarily reflect changes in blood oxygenation at the tissue level. We compared the calf muscle BOLD response of patients with peripheral arterial occlusive disease (PAOD) to that of an age-matched non-PAOD group during postischemic reactive hyperemia. METHODS AND RESULTS: PAOD patients (n=17) with symptoms of intermittent calf claudication and an age-matched non-PAOD group (n=11) underwent T2*-weighted single-shot multiecho planar imaging on a whole-body magnetic resonance scanner at 1.5 T. Muscle BOLD MRI of the calf was performed during reactive hyperemia provoked by a cuff-compression paradigm. T2* maps were generated with an automated fitting procedure. Maximal T2* change (deltaT2*(max)) and time to peak to reach deltaT2*(max) for gastrocnemius, soleus, tibial anterior, and peroneal muscle were evaluated. Compared with the non-PAOD group, patients revealed significantly lower deltaT2*(max)-values, with a mean of 7.3+/-5.3% versus 13.1+/-5.6% (P<0.001), and significantly delayed time-to-peak values, with a mean of 109.3+/-79.3 versus 32.2+/-13.3 seconds (P<0.001). CONCLUSIONS: T2* time courses of the muscle BOLD MRI signal during postocclusive reactive hyperemia revealed statistically significant differences in the key parameters (deltaT2*(max); time to peak) in PAOD patients compared with age-matched non-PAOD controls.

Aged↗

Intraarterial MR angiography and DSA in patients with peripheral arterial occlusive disease: prospective comparison.

PURPOSE: To prospectively evaluate the accuracy of intraarterial magnetic resonance (MR) angiography in the depiction of significant stenoses and occlusions, with intraarterial digital subtraction angiography (DSA) serving as the reference standard. MATERIALS AND METHODS: Approval of the local ethics committee and informed consent were obtained. Twenty patients (11 men; nine women; age range, 48-86 years; mean age, 69.5 years+/-11.2 [standard deviation]) with symptomatic peripheral arterial occlusive disease (PAOD) were prospectively enrolled. After percutaneous transluminal angioplasty (PTA), intraarterial MR angiography was performed in the thigh and the calf with a 1.5-T MR imager in two consecutive runs. Intraarterial MR angiography was performed with a low-dose injection protocol (ie, two 20-mL injections of a 50-mmol gadolinium-based contrast agent). Moderate stenoses (luminal narrowing 50%) or vessel occlusions; 95% confidence intervals (CIs) were calculated for sensitivity and specificity. RESULTS: Intraarterial DSA revealed 78 moderate stenoses, 57 significant stenoses, and 28 occlusions. Sensitivity, specificity, and accuracy of intraarterial MR angiography in the characterization of significant stenoses or occlusions were 92% (95% CI: 72%, 99%), 94% (95% CI: 82%, 98%), and 93%, respectively, in femoropopliteal arteries and 93% (95% CI: 83%, 98%), 71% (95% CI: 51%, 86%), and 86%, respectively, in infrapopliteal arteries. The main artifact observed with intraarterial MR angiography was venous contamination (12%). CONCLUSION: Intraarterial MR angiography is an accurate method used to depict significant stenoses and occlusions in lower extremity arteries with a low-dose injection protocol.

Aged↗

A polymer-based MR-compatible guidewire: a study to explore new prospects for interventional peripheral magnetic resonance angiography (ipMRA).

PURPOSE: To introduce a newly developed polymer-based and magnetic resonance (MR)-compatible guidewire and to explore its capabilities with respect to interventional peripheral magnetic resonance angiography (ipMRA) in a flow phantom. MATERIALS AND METHODS: The guidewire is based on a polyetheretherketone (PEEK) polymer core, and small iron particles are embedded in its coating. A passive device tracking technique was designed utilizing a susceptibility artifact induced by the wire in images acquired with a balanced steady-state free precession (b-SSFP) sequence using small flip angles. The position of the guidewire tip was determined from image intensity maxima and overlayed onto a roadmap in near real-time. Guidewire tracking and balloon angioplasty of an artificial stenosis were attempted in two configurations of a flow phantom. RESULTS: Successful passive guidewire tracking was performed for all phantom configurations. Robustness and accuracy of the tracking technique were sufficient for phantom studies. A balloon catheter was placed into the stenosis using the guidewire under complete MR guidance, and subsequent balloon angioplasty yielded improved flow conditions. CONCLUSION: The new guidewire is well-suited for clinical application due to an absence of the risk of core fracture and its atraumatic flexible tip. It opens novel prospects for the realization of ipMRA in humans that need to be explored in further studies.

Angiography, Digital Subtraction↗

Mapping continuous neuronal activation without an ON-OFF paradigm: initial results of BOLD ceiling fMRI.

Standard functional magnetic resonance imaging (fMRI) requires alternations between activation (ON) and baseline (OFF) periods to map the haemodynamic response to neuronal activation. Consequently, standard fMRI cannot map continuous activations in conditions like tinnitus without an ON-OFF paradigm. We present a novel approach to fMRI that allows mapping of continuous neuronal activation. Compared with standard fMRI, we introduced the application of CO(2) as potent vasodilator. CO(2) induces a 'global' blood oxygenation level-dependent (BOLD) response. The neurovascular coupling in conjunction with the limited cerebral vasodilation implies a limitation or ceiling of the BOLD response. We hypothesize that active areas exhibit a reduced CO(2)-induced DeltaBOLD due to pre-existing 'local' task-induced BOLD response. This putative reduction in DeltaBOLD might be exploited for mapping of continuous neuronal activation. BOLD ceiling fMRI was tested in the auditory system. Six healthy subjects performed three runs: only continuous monaural auditory; only 10% CO(2); simultaneous auditory and CO(2) stimulation. First, we demonstrated the ceiling of DeltaBOLD during continuous auditory activation. According to the known predominantly contralateral auditory processing, monaural auditory stimulation reduced predominantly contralateral (0.41 +/- 0.13%; P < 0.00001) and significantly less (P < 0.0001) ipsilateral DeltaBOLD (0.33 +/- 0.17%; P < 0.00001). The non-auditory area was not affected. Second, this BOLD ceiling was exploited to generate an initial activation map of continuous auditory activation (ON period). In contrast to standard fMRI, an OFF period without neuronal activation was not required. BOLD ceiling fMRI is proposed as a complement to standard fMRI for those conditions where ON-OFF paradigms are impossible.

Acoustic Stimulation↗

MR angiography of the hand with subsystolic cuff-compression optimization of injection parameters.

OBJECTIVE: The purpose of our study was to assess the impact of various injection rates on contrast-enhanced high-resolution 3D MR angiography of the hand. MATERIALS AND METHODS: Ten healthy individuals (mean age, 24.4 years; range, 20-27 years) underwent 3D contrast-enhanced MR angiography of both hands. Starting 3 minutes before data acquisition, subsystolic upper arm cuff compression was applied unilaterally. A 1.5-T whole-body scanner with 3D gradient-echo sequence was used. Seven data sets (20 seconds) were obtained consecutively. I.v. contrast material of 0.1 mg/kg of body weight of gadobutrol was injected at rates of 0.5, 1.0, and 1.5 mL/s. For both hands, quantitative data evaluation was performed with contrast-to-noise ratio (CNR) in the radial, ulnar, palmar, and digital arteries and veins. Qualitative assessment of the arterial visualization score and venous contamination score was rated by two experienced radiologists using a 4-point scale. RESULTS: The lowest venous contamination score (CNR and reviewers' assessment) was observed with an injection rate of 0.5 mL/s (p < 0.05). For the arterial signal, the reviewers' assessment was that an injection rate of 0.5 mL/s was best (p = 0.08). Compression yielded a significantly lower venous contamination score for the compressed side than for the noncompressed side for flow rates of 0.5 mL/s and 1.0 mL/s (p < 0.05). CONCLUSION: Image quality of hand MR angiography was better with cuff compression. A flow rate of 0.5 mL/s yielded a good CNR and a significantly lower venous contamination score than the other flow rates.

Adult↗

Fluoroscopic contrast-enhanced MR angiography with a magnetization-prepared steady-state free precession technique in peripheral arterial occlusive disease.

OBJECTIVE: The objective of our study was to evaluate the feasibility of intraarterial (IA) near-real-time contrast-enhanced MR angiography (CE-MRA) with a frame rate of 1.3 frames per second in seven patients with lower extremity peripheral arterial occlusive disease (PAOD). For optimized background suppression, a modified 2D steady-state free precession (SSFP) technique with magnetization preparation and mask subtraction was developed. The femoropopliteal and infrapopliteal arteries were covered in two separate steps. Acceptable contrast-to-noise ratios were obtained, and road maps were reconstructed from the same data set. CONCLUSION: Mastering IA near-real-time CE-MRA, including road map reconstruction, with an SSFP technique in the lower extremity of patients with PAOD is an important building block toward successfully performing endovascular catheter MR-guided interventions.

Aged↗

Intraarterial versus IV gadolinium injections for MR angiography: quantitative and qualitative assessment of the infrainguinal arteries.

OBJECTIVE: Our purpose was to quantitatively and qualitatively compare 3D intraarterial (IA) gadolinium-enhanced MR angiography (IA MRA) versus the standard of reference of MR angiography, 3D IV gadolinium-enhanced MR angiography (IV MRA), in patients with peripheral arterial occlusive disease (PAOD) for use during catheter-based MR-guided endovascular interventions. CONCLUSION: IA MRA provides image quality of the infrainguinal arteries in PAOD patients comparable to IV MRA with a significantly improved assessment of the infrapopliteal arteries due to reduced venous contamination. Further benefits of IA MRA include usage of only very low doses of gadolinium and simplified bolus timing.

Aged↗

Lower extremity: low-dose contrast agent intraarterial MR angiography in patients--initial results.

Institutional review board approval and patient consent were obtained. A low-dose injection protocol for intraarterial three-dimensional (3D) gadolinium-enhanced magnetic resonance (MR) angiography was derived from femoral flow phantom studies and prospectively evaluated in patients with peripheral arterial occlusive disease (PAOD). All MR angiograms were obtained at 1.5 T with a T1-weighted gradient-echo sequence. MR angiograms of a gadolinium dilution series (0.8-200.0 mmol/L) were acquired in a femoral phantom at different flow rates. Signal-to-noise ratios (SNRs) above the 75% threshold of the measured maximum were considered optimal. The lowest optimal concentration was injected intraarterially in nine patients to obtain 3D MR angiograms of the thigh and calf station. Contrast-to-noise ratios (CNRs) were calculated for four arterial segments. The low optimal concentration of 50 mmol/L (20-mL bolus volume), about 5% of the total permissible dose, showed SNRs larger than the 75% threshold in the phantom study. In patients, this concentration led to high-spatial-resolution angiograms with mean CNRs of 70.0 +/- 14.5 (+/- standard deviation) for the superficial femoral artery and 47.5 +/- 13.4 at the infrapopliteal level. Low-dose contrast agent intraarterial 3D MR angiography showed high arterial enhancement, enabling assessment of lower extremity arteries in patients with PAOD and multiple injections--a crucial precondition for MR-guided endovascular interventions.

Aged↗

Infragenual cuff-compression reduces venous contamination in contrast-enhanced MR angiography of the calf.

PURPOSE: To reduce venous contamination at the calf level in three-dimensional contrast-enhanced MR angiography (CE-MRA) by applying continuous infragenual cuff-compression. MATERIALS AND METHODS: Ten patients with clinically relevant peripheral arterial occlusive disease (PAOD) underwent dynamic three-dimensional CE-MRA of the calf. Six consecutive measurements were acquired with the first measurement serving as mask. Cuff-compression of 50 mmHg was attached below the knee. To allow intra-individual comparison, compression was applied unilaterally. The cuff was inflated three minutes before scanning and was continued throughout the MRA session. Venous contamination and arterial visualization scores were ranked using a five-point rating scale. Contrast-to-noise ratios (CNRs) of superficial enhancing calf-veins on the uncompressed and compressed calf sides were evaluated. An asymmetry index (AI) defined by CNR(mean) (uncompressed)/CNR(mean) (compressed) was introduced to describe the ratio in venous contrast agent supply between both sides quantitatively. RESULTS: Three-dimensional CE-MRA of the calves demonstrated significantly lower superficial venous contamination scores (P < 0.004) and clearly improved arterial visualization (P < 0.009) on the compressed side. Additionally, AI values were larger than 1 (P < 0.02), indicating a higher contrast agent supply in the superficial veins on the uncompressed side. CONCLUSION: Infragenual cuff-compression minimizes venous overlay in three-dimensional CE-MRA at calf level by reduction of contrast agent supply in the superficial veins.

Aged↗

Quantitative evaluation of susceptibility and shielding effects of nitinol, platinum, cobalt-alloy, and stainless steel stents.

The purpose of this study is to quantitatively estimate the shielding and susceptibility effects of commonly used metallic stents on MR signal. Two experiments were performed using a 3D gradient echo sequence with short TE to image a stent phantom: 1) short TR and high flip angle (contrast enhanced MRA parameters), and 2) long TR (TR >> T(1)) and low flip angle. The factor characterizing susceptibility effects was estimated from the signal phase of the first experiment, and then the factor characterizing the shielding effects was derived from the second experiment. Susceptibility induced signal loss was negligible (<1%) for nonstainless-steel (nitinol, platinum, and cobalt-alloy) stents and totally destructive (100%) for the stainless steel stent. Signal loss due to RF shielding was 31-62% for nitinol stents, 14-50% for platinum stents, 50-77% for the cobalt-alloy stents (undetermined for the stainless steel stent), varied with stent orientation, diameter, and wall geometry. In summary, stents made of nitinol, platinum, and cobalt-alloy have negligible susceptibility effects but stents made of stainless steel may have complete dephasing. All stents have substantial shielding effects, which vary with composition, geometry, and orientation. Large platinum stents may have the smallest artifacts and are the best suited for postinterventional MR imaging.

Alloys↗

Detection of the non-steroidal anti-inflammatory drug niflumic acid in humans: a combined 19F-MRS in vivo and in vitro study.

This study describes for the first time results of a (19)F-MRS study on humans exposed to the fluorinated non-steroidal anti-inflammatory drug niflumic acid. The accumulation and elimination of this commercially available selective prostaglandin synthase inhibitor is studied after an oral bolus in the human liver, in blood plasma and in urine samples. The in vivo spectra of the liver display two resonances with a similar increase in signal intensity during the investigation period of 240 min. One resonance refers to the parent compound niflumic acid (P), whereas the second resonance corresponds to a metabolite (M1) formed by the biotransformation by liver enzymes. The spectroscopic comparison with model compounds suggests 4'-hydroxyniflumic acid as the metabolite. During the entire experiment the concentration ratios of these resonances (P/M1) ranged between 0.7 and 0.9, indicating a high metabolite concentration most probably due to an efficient first pass metabolism. Both resonances (P, M1) were observed in the in vitro study of the blood plasma samples after plasma protein denaturation. However, in comparison to the liver spectra, the amount of the metabolite M1 is very small with a P/M1-ratio of 36.6 after 90 min and 16.1 after the end of measurement. This finding suggests an efficient biliary excretion of the metabolite M1, which bypasses the blood circulation system. Both resonances are also identified in the native urine samples. The signal intensity of the parent compound dominates the spectra of all urine samples, whereas the signal intensity of M1 increases slowly reaching a similar value to the parent compound P at the end of the measurement. This observation demonstrates an effective renal elimination of niflumic acid and suggests the existence of an enterohepatic circuit with a re-entry mechanism for the biliary excreted metabolite M1. In the urine spectra, an additional metabolite M2 is found. This resonance exhibits a low but constant signal intensity. The chemical origin of this metabolite is unclear.

Administration, Oral↗

Sustained blood oxygenation and volume response to repetition rate-modulated sound in human auditory cortex.

The blood oxygen level-dependent (BOLD) signal time course in the auditory cortex is characterized by two components, an initial transient peak and a subsequent sustained plateau with smaller amplitude. Because the T(2)(*) signal detected by functional magnetic resonance imaging (fMRI) depends on at least two counteracting factors, blood oxygenation and volume, we examined whether the reduction in the sustained BOLD signal results from decreased levels of oxygenation or from increased levels of blood volume. We used conventional fMRI to quantify the BOLD signal and fMRI in combination with superparamagnetic contrast agent to quantify blood volume and employed repetition rate-modulated sounds in a silent background to manipulate the response amplitude in the auditory cortex. In the BOLD signal, the initial peak reached 3.3% with pulsed sound and 1.9% with continuous sound, whereas the sustained BOLD signal fell to 2.2% with pulsed sound and to 0.5% with continuous sound, respectively. The repetition rate-dependent reduction in the sustained BOLD amplitude was accompanied by concordant changes in sustained blood volume levels, which, compared to silence, increased by approximately 30% with pulsed and by approximately 10% with continuous sound. Thus, our data suggest that the reduced amplitude of the sustained BOLD signal reflects stimulus-dependent modulation of blood oxygenation rather than blood volume-related effects.

Acoustic Stimulation↗

Neural processing of auditory looming in the human brain.

Acoustic intensity change, along with interaural, spectral, and reverberation information, is an important cue for the perception of auditory motion. Approaching sound sources produce increases in intensity, and receding sound sources produce corresponding decreases. Human listeners typically overestimate increasing compared to equivalent decreasing sound intensity and underestimate the time to contact of approaching sound sources. These characteristics could provide a selective advantage by increasing the margin of safety for response to looming objects. Here, we used dynamic intensity and functional magnetic resonance imaging to examine the neural underpinnings of the perceptual priority for rising intensity. We found that, consistent with activation by horizontal and vertical auditory apparent motion paradigms, rising and falling intensity activated the right temporal plane more than constant intensity. Rising compared to falling intensity activated a distributed neural network subserving space recognition, auditory motion perception, and attention and comprising the superior temporal sulci and the middle temporal gyri, the right temporoparietal junction, the right motor and premotor cortices, the left cerebellar cortex, and a circumscribed region in the midbrain. This anisotropic processing of acoustic intensity change may reflect the salience of rising intensity produced by looming sources in natural environments.

Adult↗

Spatiotemporal pattern of neural processing in the human auditory cortex.

The principles that the auditory cortex uses to decipher a stream of acoustic information have remained elusive. Neural responses in the animal auditory cortex can be broadly classified into transient and sustained activity. We examined the existence of similar principles in the human brain. Sound-evoked, blood oxygen level-dependent signal response was decomposed temporally into independent transient and sustained constituents, which predominated in different portions-core and belt-of the auditory cortex. Converging with unit recordings, our data suggest that this spatiotemporal pattern in the auditory cortex may represent a fundamental principle of analyzing sound information.

Acoustic Stimulation↗

fMRI of the auditory cortex in patients with unilateral carotid artery steno-occlusive disease.

PURPOSE: To examine whether an internal carotid artery (ICA) steno-occlusive disease leads to a reduced blood oxygenation level dependent (BOLD)-signal change due to a decreased vasodilatory reserve capacity. MATERIALS AND METHODS: Patients suffering from unilateral ICA stenosis or occlusion were examined using functional magnetic resonance imaging (fMRI) of the auditory cortex with a bilateral stimulation applying a pulsed 1000 Hz sine-tone. RESULTS: Compared to control subjects, who showed symmetric bilateral BOLD-responses within the auditory cortex, the ICA patients revealed either a normal bilateral cortical activation pattern or a reduced cortical activation on the steno-occluded side. This latter decrease of BOLD-signal change might indicate a depressed vasomotor reserve capacity. The observed coincidence between this asymmetric reduction in BOLD-signal and ischemic borderzone lesions on the affected side in this subgroup of patients strongly supports this assumption. CONCLUSION: This study shows that fMRI of the auditory cortex appears to have clinical merit in the workup of cerebrovascular conditions.

Acoustic Stimulation↗