Gunnar Krüger

Physiological Noise in Oxygenation-Sensitive Magnetic Resonance Imaging

The physiological noise in the resting brain, which arises from fluctuations in metabolic‐linked brain physiology and subtle brain pulsations, was investigated in six healthy volunteers using oxygenation‐sensitive dual‐echo spiral MRI at 3.0 T. In contrast to the system and thermal noise, the physiological noise demonstrates a signal strength dependency and, unique to the metabolic‐linked noise, an echo‐time dependency. Variations of the MR signal strength by changing the flip angle and echo time allowed separation of the different noise components and revealed that the physiological noise at 3.0 T (1) exceeds other noise sources and (2) is significantly greater in cortical gray matter than in white matter regions. The SNR in oxygenation‐sensitive MRI is predicted to saturate at higher fields, suggesting that noise measurements of the resting brain at 3.0 T and higher may provide a sensitive probe of functional information. Magn Reson Med 46:631–637, 2001.

Neuroimaging at 1.5 T and 3.0 T: Comparison of Oxygenation-Sensitive Magnetic Resonance Imaging

Noise properties, the signal‐to‐noise ratio (SNR), contrast‐to‐noise ratio (CNR), and signal responses were compared during functional activation of the human brain at 1.5 and 3.0 T. At the higher field spiral gradient‐echo (GRE) brain images revealed an average gain in SNR of 1.7 in fully relaxed and 2.2 in images with a repetition time (TR) of 1.5 sec. The tempered gain at longer TRs reflects the fact that the physiological noise depends on the signal strength and becomes a larger fraction of the total noise at 3.0 T. Activation of the primary motor and visual cortex resulted in a 36% and 44% increase of “activated pixels” at 3.0 T, which reflects a greater sensitivity for the detection of activated gray matter at the higher field. The gain in the CNR exhibited a dependency on the underlying tissue, i.e., an increase of 1.8× in regions of particular high activation‐induced signal changes (presumably venous vessels) and of 2.2× in the average activated areas. These results demonstrate that 3.0 T provides a clear advantage over 1.5 T for neuroimaging of homogeneous brain tissue, although stronger physiological noise contributions, more complicated signal features in the proximity of strong susceptibility gradients, and changes in the intrinsic relaxation times may mediate the enhancement. Magn Reson Med 45:595–604, 2001.

Changes of cerebral blood flow, oxygenation, and oxidative metabolism during graded motor activation.

In the present studies fMRI and a hypercapnic calibration procedure were used to monitor simultaneous changes in cerebral blood flow (CBF), cerebral blood oxygenation, and cerebral metabolic rate of oxygen (CMRO(2)) during activation in the sensorimotor cortex. In the first set of experiments seven volunteers performed bilateral, self-paced finger tapping and in the second set of experiments six volunteers performed bilateral finger tapping with six different frequencies (0.5-3 Hz). During the latter task relative CBF and BOLD signal intensity changes varied linearly as a function of stimulus frequency. In good agreement with recent PET and fMRI data increases in CMRO(2) were smaller than the corresponding changes in CBF during self-paced finger tapping and at all levels of graded motor activation. At a single level of activation and during graded activation there was a positive linear relationship between CBF and CMRO(2) with ratios of approximately 3:1. Comparable proportionality constants have been found in the visual cortex and primary sensory cortex, indicating similarities between the relationship of CBF and CMRO(2) in various cortical regions.

Assessment of cerebrovascular reactivity with functional magnetic resonance imaging: comparison of CO2 and breath holding

Cerebral blood flow (CBF) and oxygenation changes following both a simple breath holding test (BHT) and a CO(2) challenge can be detected with functional magnetic resonance imaging techniques. The BHT has the advantage of not requiring a source of CO(2) and acetazolamide and therefore it can easily be performed during a routine MR examination. In this study we compared global hemodynamic changes induced by breath holding and CO(2) inhalation with blood oxygenation level dependent (BOLD) and CBF sensitized fMRI techniques. During each vascular challenge BOLD and CBF signals were determined simultaneously with a combined BOLD and flow-sensitive alternating inversion recovery (FAIR) pulse sequence. There was a good correlation between the global BOLD signal intensity changes during breath holding and CO(2) inhalation supporting the notion that the BHT is equivalent to CO(2) inhalation in evaluating the hemodynamic reserve capacity with BOLD fMRI. In contrast, there was no correlation between relative CBF changes during both vascular challenges, which was probably due to the reduced temporal resolution of the combined BOLD and FAIR pulse sequence.

Regional Variability of Cerebral Blood Oxygenation Response to Hypercapnia

In functional magnetic resonance imaging studies changes in blood oxygenation level-dependent (BOLD) signal intensities during task activation are related to multiple physiological parameters such as cerebral blood flow, volume, and oxidative metabolism, as well as to the regional microvascular anatomy. Consequently, the magnitude of activation-induced BOLD signal changes may vary regionally and between subjects. The aim of this study was to use a uniform global stimulus such as hypercapnia to quantitatively investigate the regional BOLD response in the human brain. In 10 healthy volunteers, T2*-weighted gradient echo images were acquired for a total dynamic scanning time of 9 min during alternating periods of breath holding for 30 s after expiration and self-paced normal breathing for 60 s. Hypercapnia-induced BOLD signal changes in the sensorimotor cortex, frontal cortex, basal ganglia, visual cortex, and cerebellum were significantly different (P < 0.001) and varied from 1.8 to 5.1%. The highest BOLD signal changes were found in the cerebellum and visual cortex, whereas the lowest BOLD signal increase was observed in the frontal cortex. These results demonstrate a regional dependence of the BOLD signal changes during breath hold-induced hypercapnia, indirectly supporting the notion of regional different sensitivities of BOLD responses to task activation.

Assessment of cerebral oxidative metabolism with breath holding and fMRI

Carbon dioxide inhalation can be used to map changes in cerebral metabolic rate of oxygen (CMRO2) during neuronal activation with functional MRI (fMRI). A hypercapnic stress also can be achieved with a simple breath‐holding test. Using this test as means of manipulating cerebral blood flow (CBF) independent of CMRO2, we assessed changes in CMRO2 during visual stimulation. With this task, CBF increased by 61 ± 7%, whereas CMRO2 changed by 2.43 ± 4.97%. These results are in good agreement with previous positron emission tomographic (PET) data, indicating that changes in oxidative metabolism during focal neuronal activity can potentially be determined with the breath‐holding test. This test could easily be performed during a routine MRI examination. Magn Reson Med 42:608–611, 1999.

Gender Differences in Cerebral Blood Flow and Oxygenation Response during Focal Physiologic Neural Activity

Using functional magnetic resonance imaging techniques CBF and oxygenation changes were measured during sustained checkerboard stimulation in 38 right-handed healthy volunteers (18 men and 20 women). The average blood oxygenation level dependent (BOLD) contrast technique signal intensity change was 1.67 ± 0.6% in the group of male volunteers and 2.15 ± 0.6% in the group of female volunteers (P < .05). Baseline regional CBF (rCBF) values in activated gray matter areas within the visual cortex were 57 ± 1 mL · 100 g−1 · min−1 in women and 50 ± 12 mL · 100 g−1 · min−1 in men, respectively (P = .09). Despite a broad overlap between both groups the rCBF increase was significantly higher in women compared to men (33 ± 5 mL · 100 g−1 · min−1 versus 28 ± 4 mL · 100 g−1 · min−1, P < .01). The increase of rCBF was not correlated with the baseline rCBF (mL · 100 g−1 · min−1) (rs = 0.01, P = .9). Moreover, changes of rCBF were not correlated with changes in BOLD signal intensities (rs = 0.1, P = .7). Enhanced rCBF response in women during visual stimulation could be related to gender differences in visual physiology or may reflect gender differences in the vascular response to focal neuronal activation. Gender differences must be considered when interpreting the results of functional magnetic resonance imaging studies.

Simultaneous monitoring of dynamic changes in cerebral blood flow and oxygenation during sustained activation of the human visual cortex.

Functional neuroimaging was used to investigate the effect of cerebral blood flow (CBF) adjustments on the blood oxygenation level dependent (BOLD) signal during visual stimulation. Temporal responses from both oxygenation- and perfusion-sensitized MRI revealed almost identical features during onset and ongoing activation, i.e. an activation-induced signal rise, and a gradual signal decrease during prolonged activation (overshoot). However, the post-stimulus responses exhibited a pronounced BOLD signal drop below prestimulus baseline (undershoot), but a rather rapid normalisation of the related CBF signal. Thus, an activation-induced initial BOLD signal rise and a gradual signal decrease reflect a coarse upregulation of CBF, which is followed by fine-tuning adjustments of flow. Regulations of other involved physiological parameters, including blood volume and oxidative metabolism give rise to a negative post-stimulus BOLD signal response.

Relationship between cerebral blood flow changes during visual stimulation and baseline flow levels investigated with functional MRI

Using fMRI, the relationship between regional cerebral blood flow (rCBF) changes during visual stimulation and the prevailing baseline global and regional flow levels was evaluated in 22 volunteers. The absolute increase in rCBF was not correlated with baseline rCBF values (r = 0.01, p = 0.8); however, the percentage change in rCBF showed a negative correlation (r=-0.78, p<0.001). Both absolute and relative changes in rCBF were independent of baseline global CBF values. These results indicate that caution should be exercised when comparing relative flow changes during focal brain activation, especially in functional neuroimaging studies dealing with altered baseline flow values.