How tissue fluidity influences brain tumor progression.

Mechanical properties of biological tissues and, above all, their solid or fluid behavior influence the spread of malignant tumors. While it is known that solid tumors tend to have higher mechanical rigidity, allowing them to aggressively invade and spread in solid surrounding healthy tissue, it is unknown how softer tumors can grow within a more rigid environment such as the brain. Here, we use in vivo magnetic resonance elastography (MRE) to elucidate the role of anomalous fluidity for the invasive growth of soft brain tumors, showing that aggressive glioblastomas (GBMs) have higher water content while behaving like solids. Conversely, our data show that benign meningiomas (MENs), which contain less water than brain tissue, are characterized by fluid-like behavior. The fact that the 2 tumor entities do not differ in their soft properties suggests that fluidity plays an important role for a tumor's aggressiveness and infiltrative potential. Using tissue-mimicking phantoms, we show that the anomalous fluidity of neurotumors physically enables GBMs to penetrate surrounding tissue, a phenomenon similar to Saffman-Taylor viscous-fingering instabilities, which occur at moving interfaces between fluids of different viscosity. Thus, targeting tissue fluidity of malignant tumors might open horizons for the diagnosis and treatment of cancer.

Progressive supranuclear palsy and idiopathic Parkinson's disease are associated with local reduction of in vivo brain viscoelasticity.

OBJECTIVES: To apply three-dimensional multifrequency MR-elastography (3DMRE) for the measurement of local cerebral viscoelasticity changes in patients with Parkinson's disease (PD) and progressive supranuclear palsy (PSP). METHODS: T1-weighted anatomical imaging and 3DMRE were performed in 17 PD and 20 PSP patients as well as 12 controls. Two independent viscoelasticity parameters, |G*| and φ, were reconstructed combining seven harmonic vibration frequencies (30-60 Hz). Spatially averaged values were compared by one-way ANOVA, groups were compared using unpaired t test and Mann-Whitney test, respectively. Correlation between clinical data and parameters of brain elasticity and volume were calculated by Pearson's correlation coefficient. RESULTS: In patients, |G*| was significantly reduced in the frontal and mesencephalic regions (p < 0.05). Beyond that, reduced mesencephalic |G*| discriminated PSP from PD (p < 0.05). Neurodegeneration causes significant brain atrophy (p < 0.01) and is pronounced in PSP patients (p < 0.05 vs. PD). Reduced brain viscoelasticity is correlated with brain atrophy in PSP (r=0.64, p=0.002) and PD (r=0.65, p=0.005) patients but not in controls. CONCLUSIONS: MRE-measured viscoelasticity reflects local structural changes of brain tissue in PSP and in PD and provides a useful parameter to differentiate neurodegenerative movement disorders based on imaging examinations. KEY POINTS: • 3D multifrequency MR-elastography reveals diffuse regional changes in brain viscoelasticity in neurodegenerative disorders. • Reduced mesencephalic viscoelasticity separates PD and PSP. • Reduced brain viscoelasticity and brain atrophy as independent hallmarks of neurodegeneration hypothesized.

Neuron-Specific Enolase Predicts Poor Outcome After Cardiac Arrest and Targeted Temperature Management: A Multicenter Study on 1,053 Patients.

OBJECTIVE: Outcome prediction after cardiac arrest is important to decide on continuation or withdrawal of intensive care. Neuron-specific enolase is an easily available, observer-independent prognostic biomarker. Recent studies have yielded conflicting results on its prognostic value after targeted temperature management. DESIGN, SETTING, AND PATIENTS: We analyzed neuron-specific enolase serum concentrations 3 days after nontraumatic in-hospital cardiac arrest and out-of-hospital cardiac arrest and outcome of patients from five hospitals in Germany, Austria, and Italy. Patients were treated at 33°C for 24 hours. Cerebral Performance Category was evaluated upon ICU discharge. We performed case reviews of good outcome patients with neuron-specific enolase greater than 90 µg/L and poor outcome patients with neuron-specific enolase less than or equal to 17 µg/L (upper limit of normal). MEASUREMENTS AND MAIN RESULTS: A neuron-specific enolase serum concentration greater than 90 µg/L predicted Cerebral Performance Category 4-5 with a positive predictive value of 99%, false positive rate of 0.5%, and a sensitivity of 48%. All three patients with neuron-specific enolase greater than 90 µg/L and Cerebral Performance Category 1-2 had confounders for neuron-specific enolase elevation. An neuron-specific enolase serum concentration less than or equal to 17 µg/L excluded Cerebral Performance Category 4-5 with a negative predictive value of 92%. The majority of 14 patients with neuron-specific enolase less than or equal to 17 µg/L who died had a cause of death other than hypoxic-ischemic encephalopathy. Specificity and sensitivity for prediction of poor outcome were independent of age, sex, and initial rhythm but higher for out-of-hospital cardiac arrest than for in-hospital cardiac arrest patients. CONCLUSION: High neuron-specific enolase serum concentrations reliably predicted poor outcome at ICU discharge. Prediction accuracy differed and was better for out-of-hospital cardiac arrest than for in-hospital cardiac arrest patients. Our "in-the-field" data indicate 90 µg/L as a threshold associated with almost no false positives at acceptable sensitivity. Confounders of neuron-specific enolase elevation should be actively considered: neuron-specific enolase-producing tumors, acute brain diseases, and hemolysis. We strongly recommend routine hemolysis quantification. Neuron-specific enolase serum concentrations less than or equal to 17 µg/L argue against hypoxic-ischemic encephalopathy incompatible with reawakening.

Multifrequency magnetic resonance elastography of the brain reveals tissue degeneration in neuromyelitis optica spectrum disorder.

OBJECTIVES: Application of multifrequency magnetic resonance elastography (MMRE) of the brain parenchyma in patients with neuromyelitis optica spectrum disorder (NMOSD) compared to age matched healthy controls (HC). METHODS: 15 NMOSD patients and 17 age- and gender-matched HC were examined using MMRE. Two three-dimensional viscoelastic parameter maps, the magnitude |G*| and phase angle φ of the complex shear modulus were reconstructed by simultaneous inversion of full wave-field data in 1.9-mm isotropic resolution at 7 harmonic drive frequencies from 30 to 60 Hz. RESULTS: In NMOSD patients, a significant reduction of |G*| was observed within the white matter fraction (p = 0.017), predominantly within the thalamic regions (p = 0.003), compared to HC. These parameters exceeded the reduction in brain volume measured in patients versus HC (p = 0.02 whole-brain volume reduction). Volumetric differences in white matter fraction and the thalami were not detectable between patients and HC. However, phase angle φ was decreased in patients within the white matter (p = 0.03) and both thalamic regions (p = 0.044). CONCLUSIONS: MMRE reveals global tissue degeneration with accelerated softening of the brain parenchyma in patients with NMOSD. The predominant reduction of stiffness is found within the thalamic region and related white matter tracts, presumably reflecting Wallerian degeneration. KEY POINTS: • Magnetic resonance elastography reveals diffuse cerebral tissue changes in patients with NMOSD. • Premature tissue softening in NMOSD patients indicates tissue degeneration. • Hypothesis of a widespread cerebral neurodegeneration in form of diffuse tissue alteration.

Higher-resolution MR elastography reveals early mechanical signatures of neuroinflammation in patients with clinically isolated syndrome.

PURPOSE: To assess if higher-resolution magnetic resonance elastography (MRE) is a technique that can measure the in vivo mechanical properties of brain tissue and is sensitive to early signatures of brain tissue degradation in patients with clinically isolated syndrome (CIS). MATERIALS AND METHODS: Seventeen patients with CIS and 33 controls were investigated by MRE with a 3T MRI scanner. Full-wave field data were acquired at seven drive frequencies from 30 to 60 Hz. The spatially resolved higher-resolution maps of magnitude |G*| and phase angle φ of the complex-valued shear modulus were obtained in addition to springpot model parameters. These parameters were spatially averaged in white matter (WM) and whole-brain regions and correlated with clinical and radiological parameters. RESULTS: Spatially resolved MRE revealed that CIS reduced WM viscoelasticity, independent of imaging markers of multiple sclerosis and clinical scores. |G*| was reduced by 14% in CIS (1.4 ± 0.2 kPa vs. 1.7 ± 0.2 kPa, P < 0.001, 95% confidence interval [CI] [-0.4, -0.1] kPa), while φ (0.66 ± 0.04 vs. 0.67 ± 0.04, P = 0.65, 95% CI [-0.04, 0.02]) remained unaltered. Springpot-based shear elasticity showed only a trend of CIS-related reduction (3.4 ± 0.5 kPa vs. 3.7 ± 0.5 kPa, P = 0.06, 95% CI [-0.6, 0.02] kPa) in the whole brain. CONCLUSION: We demonstrate that CIS leads to significantly reduced elasticity of brain parenchyma, raising the prospect of using MRE as an imaging marker for subtle and diffuse tissue damage in neuroinflammatory diseases. J. Magn. Reson. Imaging 2016;44:51-58.

In vivo multifrequency magnetic resonance elastography of the human intervertebral disk.

PURPOSE: To test in vivo magnetic resonance elastography (MRE) of the human intervertebral disk (IVD). METHODS: The feasibility of MRE in IVD was demonstrated in ex vivo bovine disks. Sixteen asymptomatic volunteers underwent multifrequency MRE of the lumbar spine (IVD L3/4 and L4/5, n = 32) using a posterior plate transducer connected to a loudspeaker and operated at five frequencies from 50 to 70 Hz. Full wave field data were acquired in 10 transverse slices of 2 × 2 × 2 mm(3) resolution. High-resolution maps of magnitude |G*| and phase angle φ of complex shear modulus G* were generated by multifrequency dual elasto visco (MDEV) inversion. Disk morphology was assessed by the Pfirrmann score (Pf). RESULTS: Morphological Pf was 1 in 25, 2 in 3, and 3 in 4 disks. |G*| decreased with Pf by a Pearson's linear correlation coefficient of R = -0.592 (P = 0.0004), while φ remained unchanged. Group mean mechanical parameters for Pf = 1 to 3 were |G*| = 6.51 ± 1.27, 5.29 ± 0.95, 4.03 ± 0.99 kPa, and φ = 1.190 ± 0.181, 1.170 ± 0.156, 1.088 ± 0.084 rad, respectively (p[Pf1-Pf3] < 0.001). The variability of mechanical parameters in one volunteer including diurnal changes was approximately 11%. CONCLUSION: Multifrequency MRE with MDEV inversion allows measurement of in vivo mechanical properties of IVDs and may provide additional information in disc degeneration beyond standard morphological changes.

Cerebral multifrequency MR elastography by remote excitation of intracranial shear waves.

The aim of this study was to introduce remote wave excitation for high-resolution cerebral multifrequency MR elastography (mMRE). mMRE of 25-45-Hz drive frequencies by head rocker stimulation was compared with mMRE by remote wave excitation based on a thorax mat in 12 healthy volunteers. Maps of the magnitude |G*| and phase φ of the complex shear modulus were reconstructed using multifrequency dual elasto-visco (MDEV) inversion. After the scan, the subjects and three operators assessed the comfort and convenience of cerebral mMRE using two methods of stimulating the brain. Images were acquired in a coronal view in order to identify anatomical regions along the spinothalamic pathway. In mMRE by remote actuation, all subjects and operators appreciated an increased comfort and simplified procedural set-up. The resulting strain amplitudes in the brain were sufficiently large to analyze using MDEV inversion, and yielded high-resolution viscoelasticity maps which revealed specific anatomical details of brain mechanical properties: |G*| was lowest in the pons (0.97 ± 0.08 kPa) and decreased within the corticospinal tract in the caudal-cranial direction from the crus cerebri (1.64 ± 0.26 kPa) to the capsula interna (1.29 ± 0.14 kPa). By avoiding onerous mechanical stimulation of the head, remote excitation of intracranial shear waves can be used to measure viscoelastic parameters of the brain with high spatial resolution. Therewith, the new mMRE method is suitable for neuroradiological examinations in the clinic.

In vivo high-resolution magnetic resonance elastography of the uterine corpus and cervix.

OBJECTIVES: To apply 3D multifrequency MR elastography (3DMMRE) to the uterus and analyse the viscoelasticity of the uterine tissue in healthy volunteers considering individual variations and variations over the menstrual cycle. METHODS: Sixteen healthy volunteers participated in the study, one of whom was examined 12 times over two menstrual cycles. Pelvic 3DMMRE was performed on a 1.5-T scanner with seven vibration frequencies (30-60 Hz) using a piezoelectric driver. Two mechanical parameter maps were obtained corresponding to the magnitude (|G (*) |) and the phase angle (φ) of the complex shear modulus. RESULTS: On average, the uterine corpus had higher elasticity, but similar viscosity compared with the cervix, reflected by |G (*) |uterine corpus = 2.58 ± 0.52 kPa vs. |G (*) |cervix = 2.00 ± 0.34 kPa (p < 0.0001) and φ uterine corpus = 0.54 ± 0.08, φ cervix = 0.57 ± 0.12 (p = 0.428). With 2.23 ± 0.26 kPa, |G (*) | of the myometrium was lower in the secretory phase (SP) compared with that of the proliferative phase (PP, |G (*) | = 3.01 ± 0.26 kPa). For the endometrium, the value of |G (*) | in SP was 68% lower than during PP (PP, |G (*) | = 3.34 ± 0.42 kPa; SP, |G (*) | = 1.97 ± 0.34 kPa; p = 0.0061). CONCLUSION: 3DMMRE produces high-resolution mechanical parameter maps of the uterus and cervix and shows sensitivity to structural and functional changes of the endometrium and myometrium during the menstrual cycle. KEY POINTS: MR elastography provided for the first time spatially resolved viscoelasticity maps of uterus. Uterine corpus had a higher elasticity, but similar viscosity compared with cervix. The stiffness of both endometrium and myometrium decreases during the menstrual cycle.

MR elastography in a murine stroke model reveals correlation of macroscopic viscoelastic properties of the brain with neuronal density.

The aim of this study was to investigate the influence of neuronal density on viscoelastic parameters of living brain tissue after ischemic infarction in the mouse using MR elastography (MRE). Transient middle cerebral artery occlusion (MCAO) in the left hemisphere was induced in 20 mice. In vivo 7-T MRE at a vibration frequency of 900 Hz was performed on days 3, 7, 14 and 28 (n = 5 per group) after MCAO, followed by the analysis of histological markers, such as neuron counts (NeuN). MCAO led to a significant reduction in the storage modulus in the left hemisphere relative to contralateral values (p = 0.03) without changes over time. A correlation between storage modulus and NeuN in both hemispheres was observed, with correlation coefficients of R = 0.648 (p = 0.002, left) and R = 0.622 (p = 0.003, right). The loss modulus was less sensitive to MCAO, but correlated with NeuN in the left hemisphere (R = 0.764, p = 0.0001). In agreement with the literature, these results suggest that the shear modulus in the brain is reduced after transient ischemic insult. Furthermore, our study provides evidence that the in vivo shear modulus of brain tissue correlates with neuronal density. In diagnostic applications, MRE may thus have diagnostic potential as a tool for image-based quantification of neurodegenerative processes.

Alteration of brain viscoelasticity after shunt treatment in normal pressure hydrocephalus.

INTRODUCTION: Normal pressure hydrocephalus (NPH) represents a chronic neurological disorder with increasing incidence. The symptoms of NPH may be relieved by surgically implanting a ventriculoperitoneal shunt to drain excess cerebrospinal fluid. However, the pathogenesis of NPH is not yet fully elucidated, and the clinical response of shunt treatment is hard to predict. According to current theories of NPH, altered mechanical properties of brain tissue seem to play an important role. Magnetic resonance elastography (MRE) is a unique method for measuring in vivo brain mechanics. METHODS: In this study cerebral MRE was applied to test the viscoelastic properties of the brain in 20 patients with primary (N = 14) and secondary (N = 6) NPH prior and after (91 ± 16 days) shunt placement. Viscoelastic parameters were derived from the complex modulus according to the rheological springpot model. This model provided two independent parameters µ and α, related to the inherent rigidity and topology of the mechanical network of brain tissue. RESULTS: The viscoelastic parameters µ and α were found to be decreased with -25% and -10%, respectively, compared to age-matched controls (P < 0.001). Interestingly, α increased after shunt placement (P < 0.001) to almost normal values whereas µ remained symptomatically low. CONCLUSION: The results indicate the fundamental role of altered viscoelastic properties of brain tissue during disease progression and tissue repair in NPH. Clinical improvement in NPH is associated with an increasing complexity of the mechanical network whose inherent strength, however, remains degraded.

Noninvasive Detection of Intracranial Hypertension by Novel Ultrasound Time-Harmonic Elastography.

OBJECTIVE: A method for measuring intracranial pressure (ICP) noninvasively has long been sought after in neurology and neurosurgery. Treatment failure in individuals presenting with unspecific symptoms such as headache, gait disturbance, or visual impairment occurring in response to increased ICP can lead to irreversible brain injury, progressive disability, and death. Guidelines for diagnostic ICP measurement recommend intracranial placement of pressure tip catheters or lumbar puncture (LP) despite their invasiveness and possible complications. As ICP fluctuations are closely associated with changes in brain stiffness, ultrasound elastography could be a valid method to detect ICP noninvasively and with short examination times. MATERIALS AND METHODS: In this pilot study, we have investigated the use of time-harmonic shear waves, introduced into the brain by an external shaker, and measured in real-time by transtemporal ultrasound, for deducing a noninvasive imaging marker sensitive to elevated ICP. To this end, we developed cerebral ultrasound time-harmonic elastography for the noninvasive quantification of shear wave speed (SWS) as a surrogate marker of cerebral stiffness in a short examination time of a few minutes. RESULTS: We found that SWS in patients enrolled for LP with confirmed intracranial hypertension was 1.81 ± 0.10 m/s, distinguishing them from healthy volunteers with excellent diagnostic accuracy (1.55 ± 0.08 m/s; P < 0.001; area under the curve, 0.99). Interestingly, values in symptomatic patients decreased to normal stiffness immediately after LP (1.56 ± 0.06 m/s, P < 0.001). Moreover, invasively measured opening pressure correlated with SWS measured before LP and liquid volume drained through the spinal tap with the SWS difference between the 2 measurements. CONCLUSIONS: Collectively, our results suggest a tight link between cerebral stiffness and ICP and demonstrate that intracranial hypertension can be detected noninvasively within short examination times, opening avenues for diagnostic applications of cerebral ultrasound time-harmonic elastography in neurology and emergency medicine.

In vivo viscoelastic properties of the brain in normal pressure hydrocephalus.

Nearly half a century after the first report of normal pressure hydrocephalus (NPH), the pathophysiological cause of the disease still remains unclear. Several theories about the cause and development of NPH emphasize disease-related alterations of the mechanical properties of the brain. MR elastography (MRE) uniquely allows the measurement of viscoelastic constants of the living brain without intervention. In this study, 20 patients (mean age, 69.1 years; nine men, 11 women) with idiopathic (n = 15) and secondary (n = 5) NPH were examined by cerebral multifrequency MRE and compared with 25 healthy volunteers (mean age, 62.1 years; 10 men, 15 women). Viscoelastic constants related to the stiffness (µ) and micromechanical connectivity (α) of brain tissue were derived from the dynamics of storage and loss moduli within the experimentally achieved frequency range of 25-62.5 Hz. In patients with NPH, both storage and loss moduli decreased, corresponding to a softening of brain tissue of about 20% compared with healthy volunteers (p < 0.001). This loss of rigidity was accompanied by a decreasing α parameter (9%, p < 0.001), indicating an alteration in the microstructural connectivity of brain tissue during NPH. This disease-related decrease in viscoelastic constants was even more pronounced in the periventricular region of the brain. The results demonstrate distinct tissue degradation associated with NPH. Further studies are required to investigate the source of mechanical tissue damage as a potential cause of NPH-related ventricular expansions and clinical symptoms.

Time-Resolved Response of Cerebral Stiffness to Hypercapnia in Humans.

Cerebral blood flow, cerebral stiffness (CS) and intracranial pressure are tightly linked variables of cerebrovascular reactivity and cerebral autoregulation. Transtemporal ultrasound time-harmonic elastography was used for rapid measurement of CS changes in 10 volunteers before, during and after administration of a gas mixture of 95% O2 and 5% CO2 (carbogen). Within the first 2.2 ± 2.0 min of carbogen breathing, shear wave speed determined as a surrogate parameter of CS increased from 1.57 ± 0.04 to 1.66 ± 0.05 m/s (p < 0.01) in synchrony with end-tidal CO2 while post-hypercapnic CS recovery was delayed by 2.7 ± 1.4 min in relation to end-tidal CO2. Our results indicate that CS is highly sensitive to changes in CO2 levels of inhaled air. Possible mechanisms underlying the observed CS changes might be associated with cerebrovascular reactivity, cerebral blood flow adaptation and intracranial regulation, all of which are potentially relevant for future diagnostic applications of transtemporal time-harmonic elastography in a wide spectrum of neurologic diseases.

Delayed recognition of emotional facial expressions in Bell's palsy.

We investigated the impact of acute facial palsy on the recognition of emotional facial expressions. Thirty-one patients with acute facial palsy and 30 healthy controls performed a well-established test battery with tasks both for mere face recognition (FACE) and for recognition of emotional facial expressions (EMO). Participants were tested at disease onset (t1) and about eight weeks thereafter (t2). Recognition accuracy did not differ between groups in FACE and EMO tasks at t1 and t2. By contrast, mean reaction time (RT) in the EMO task was significantly longer for patients than for controls at t1 (10.228 ± 710 ms vs 7.386 ± 283 ms; p = .001), whereas RT in the FACE task did not differ between groups. Parallel to clinical remission, patient's RTs in EMO tasks decreased but remained significantly prolonged at t2. Consistent with theories of embodied cognition, our findings show that facial palsy delays recognition of emotional facial expressions but not face recognition per se. Furthermore, normal accuracy of emotion recognition suggests efficient compensatory mechanisms that preserve this essential social function. We hypothesize that deficient sensorimotor embodiment may contribute to disturbances of non-verbal communication in patients with impaired facial motricity.

RBM3 and CIRP expressions in targeted temperature management treated cardiac arrest patients-A prospective single center study.

BACKGROUND: Management of cardiac arrest patients includes active body temperature control and strict prevention of fever to avoid further neurological damage. Cold-shock proteins RNA-binding motif 3 (RBM3) and cold inducible RNA-binding protein (CIRP) expressions are induced in vitro in response to hypothermia and play a key role in hypothermia-induced neuroprotection. OBJECTIVE: To measure gene expressions of RBM3, CIRP, and inflammatory biomarkers in whole blood samples from targeted temperature management (TTM)-treated post-cardiac arrest patients for the potential application as clinical biomarkers for the efficacy of TTM treatment. METHODS: A prospective single center trial with the inclusion of 22 cardiac arrest patients who were treated with TTM (33°C for 24 hours) after ROSC was performed. RBM3, CIRP, interleukin 6 (IL-6), monocyte chemotactic protein 1 (MCP-1), and inducible nitric oxide synthase (iNOS) mRNA expressions were quantified by RT-qPCR. Serum RBM3 protein concentration was quantified using an enzyme-linked immunosorbent assay (ELISA). RESULTS: RBM3 mRNA expression was significantly induced in post-cardiac arrest patients in response to TTM. RBM3 mRNA was increased 2.2-fold compared to before TTM. A similar expression kinetic of 1.4-fold increase was observed for CIRP mRNA, but did not reached significancy. Serum RBM3 protein was not increased in response to TTM. IL-6 and MCP-1 expression peaked after ROSC and then significantly decreased. iNOS expression was significantly increased 24h after return of spontaneous circulation (ROSC) and TTM. CONCLUSIONS: RBM3 is temperature regulated in patients treated with TTM after CA and ROSC. RBM3 is a possible biomarker candidate to ensure the efficacy of TTM treatment in post-cardiac arrest patients and its pharmacological induction could be a potential future intervention strategy that warrants further research.

Timing of brain computed tomography and accuracy of outcome prediction after cardiac arrest.

AIM: Gray-white-matter ratio (GWR) calculated from head CT is a radiologic index of tissue changes associated with hypoxic-ischemic encephalopathy after cardiac arrest (CA). Evidence from previous studies indicates high specificity for poor outcome prediction at GWR thresholds of 1.10-1.20. We aimed to determine the relationship between accuracy of neurologic prognostication by GWR and timing of CT. METHODS: We included 195 patients admitted to the ICU following CA. GWR was calculated from CT radiologic densities in 16 regions of interest. Outcome was determined upon intensive care unit discharge using the cerebral performance category (CPC). Accuracy of outcome prediction of GWR was compared for 3 epochs (<6, 6-24, and >24 h after CA). RESULTS: 125 (64%) patients had poor (CPC4-5) and 70 (36%) good outcome (CPC1-3). Irrespective of timing, specificity for poor outcome prediction was 100% at a GWR threshold of 1.10. Among 50 patients with both early and late CT, GWR decreased significantly over time (p = 0.002) in patients with poor outcome, sensitivity for poor outcome prediction was 12% (7-20%) with early CTs (<6 h) and 48% (38-58%) for late CTs (>24 h). Across all patients, sensitivity of early and late CT was 17% (9-28%) and 39% (28-51%), respectively. CONCLUSION: A GWR below 1.10 predicts poor outcome (CPC4-5) in patients after CA with high specificity irrespective of time of acquisition of CT. Because GWR decreases over time in patients with severe HIE, sensitivity for prediction of poor outcome is higher for late CTs (>24 h after CA) as compared to early CTs (<6 h after CA).

Measurement of in vivo cerebral volumetric strain induced by the Valsalva maneuver.

Compressibility of biological tissues such as brain parenchyma is related to its poroelastic nature characterized by the geometry and pressure of vasculature and interconnected fluid-filled spaces. Thus, cerebral volumetric strain may be sensitive to intracranial pressure which can be altered under physiological conditions. So far volumetric strain has attained little attention in studies of the mechanical behavior of the brain. This paper reports a study of measuring the in vivo cerebral volumetric strain induced by the Valsalva maneuver (VM) where forced expiration against a closed glottis leads to a transient increase in the intracranial pressure. For this purpose we applied three-dimensional magnetic resonance imaging equipped with a patient-controlled acquisition system to five healthy volunteers. With each volunteer, three experiments were performed: one with VM and two in resting state. i.e. normal ventilation, which were conducted before and after VM. The VM data were registered to reference data by morphology based non-rigid deformation, yielding 3D maps of total displacements and volumetric strain. On average, VM induced volumetric strain correlated to whole-brain dilatation of -3.14±0.87% and -2.80±0.71% compared to the reference states before and after VM, respectively. These values were well reproduced by repetitive experiments during the same scan as well as by repeated measurements in one volunteer on different days. Combined with literature data of intracranial pressure changes, our volumetric strain values can be used to elucidate the static compression modulus of the in vivo human brain. These results add knowledge to the understanding of the brain׳s biomechanical properties under physiological conditions.

High-resolution mechanical imaging of the kidney.

The objective of this study was to test the feasibility and reproducibility of in vivo high-resolution mechanical imaging of the asymptomatic human kidney. Hereby nine volunteers were examined at three different physiological states of urinary bladder filling (a normal state, urinary urgency, and immediately after urinary relief). Mechanical imaging was performed of the in vivo kidney using three-dimensional multifrequency magnetic resonance elastography combined with multifrequency dual elastovisco inversion. Other than in classical elastography, where the storage and loss shear moduli are evaluated, we analyzed the magnitude |G(⁎)| and the phase angle φ of the complex shear modulus reconstructed by simultaneous inversion of full wave field data corresponding to 7 harmonic drive frequencies from 30 to 60Hz and a resolution of 2.5mm cubic voxel size. Mechanical parameter maps were derived with a spatial resolution superior to that in previous work. The group-averaged values of |G(⁎)| were 2.67±0.52kPa in the renal medulla, 1.64±0.17kPa in the cortex, and 1.17±0.21kPa in the hilus. The phase angle φ (in radians) was 0.89±0.12 in the medulla, 0.83±0.09 in the cortex, and 0.72±0.06 in the hilus. All regional differences were significant (P<0.001), while no significant variation was found in relation to different stages of bladder filling. In summary our study provides first high-resolution maps of viscoelastic parameters of the three anatomical regions of the kidney. |G(⁎)| and φ provide novel information on the viscoelastic properties of the kidney, which is potentially useful for the detection of renal lesions or fibrosis.

High-resolution mechanical imaging of glioblastoma by multifrequency magnetic resonance elastography.

OBJECTIVE: To generate high-resolution maps of the viscoelastic properties of human brain parenchyma for presurgical quantitative assessment in glioblastoma (GB). METHODS: Twenty-two GB patients underwent routine presurgical work-up supplemented by additional multifrequency magnetic resonance elastography. Two three-dimensional viscoelastic parameter maps, magnitude |G*|, and phase angle φ of the complex shear modulus were reconstructed by inversion of full wave field data in 2-mm isotropic resolution at seven harmonic drive frequencies ranging from 30 to 60 Hz. RESULTS: Mechanical brain maps confirmed that GB are composed of stiff and soft compartments, resulting in high intratumor heterogeneity. GB could be easily differentiated from healthy reference tissue by their reduced viscous behavior quantified by φ (0.37±0.08 vs. 0.58±0.07). |G*|, which in solids more relates to the material's stiffness, was significantly reduced in GB with a mean value of 1.32±0.26 kPa compared to 1.54±0.27 kPa in healthy tissue (P = 0.001). However, some GB (5 of 22) showed increased stiffness. CONCLUSION: GB are generally less viscous and softer than healthy brain parenchyma. Unrelated to the morphology-based contrast of standard magnetic resonance imaging, elastography provides an entirely new neuroradiological marker and contrast related to the biomechanical properties of tumors.