Arterial occlusion duration affects the cuff-induced hyperemic response in skeletal muscle BOLD perfusion imaging as shown in young healthy subjects.

OBJECTIVE: Dynamic BOLD MRI with cuff compression, inducing ischemia and post-occlusive hyperemia in skeletal muscle, has been pointed out as a potential diagnostic tool to assess peripheral limb perfusion. The objective was to explore the robustness of this technique and its sensitivity to the occlusion duration. MATERIALS AND METHODS: BOLD images were acquired at 3 T in 14 healthy volunteers. [Formula: see text]-imaging with 5- and 1.5-min occlusions were acquired and several semi-quantitative BOLD parameters were derived from ROI-based [Formula: see text]-time curves. Differences in parameters from the two different occlusion durations were evaluated in the gastrocnemius and soleus muscles using non-parametrical tests. Intra- and inter-scan repeatability were evaluated with coefficient of variation. RESULTS: Longer occlusion duration resulted in an increased hyperemic signal effect yielding significantly different values (p < 0.05) in gastrocnemius for all parameters describing the hyperemic response, and in soleus for two of these parameters. Specifically, 5-min occlusion yielded steeper hyperemic upslope in gastrocnemius (41.0%; p < 0.05) and soleus (59.7%; p = 0.03), shorter time to half peak in gastrocnemius (46.9%; p = 0.00008) and soleus (33.5%; p = 0.0003), and shorter time to peak in gastrocnemius (13.5%; p = 0.02). Coefficients of variation were lower than percentage differences that were found significant. DISCUSSION: Findings show that the occlusion duration indeed influences the hyperemic response and thus should play a part in future methodological developments.

Quantification of the Intracellular Life Time of Water Molecules to Measure Transport Rates of Human Aquaglyceroporins.

Orthodox aquaporins are transmembrane channel proteins that facilitate rapid diffusion of water, while aquaglyceroporins facilitate the diffusion of small uncharged molecules such as glycerol and arsenic trioxide. Aquaglyceroporins play important roles in human physiology, in particular for glycerol metabolism and arsenic detoxification. We have developed a unique system applying the strain of the yeast Pichia pastoris, where the endogenous aquaporins/aquaglyceroporins have been removed and human aquaglyceroporins AQP3, AQP7, and AQP9 are recombinantly expressed enabling comparative permeability measurements between the expressed proteins. Using a newly established Nuclear Magnetic Resonance approach based on measurement of the intracellular life time of water, we propose that human aquaglyceroporins are poor facilitators of water and that the water transport efficiency is similar to that of passive diffusion across native cell membranes. This is distinctly different from glycerol and arsenic trioxide, where high glycerol transport efficiency was recorded.

NMR diffusion-encoding with axial symmetry and variable anisotropy: Distinguishing between prolate and oblate microscopic diffusion tensors with unknown orientation distribution.

We introduce a nuclear magnetic resonance method for quantifying the shape of axially symmetric microscopic diffusion tensors in terms of a new diffusion anisotropy metric, DΔ, which has unique values for oblate, spherical, and prolate tensor shapes. The pulse sequence includes a series of equal-amplitude magnetic field gradient pulse pairs, the directions of which are tailored to give an axially symmetric diffusion-encoding tensor b with variable anisotropy bΔ. Averaging of data acquired for a range of orientations of the symmetry axis of the tensor b renders the method insensitive to the orientation distribution function of the microscopic diffusion tensors. Proof-of-principle experiments are performed on water in polydomain lyotropic liquid crystals with geometries that give rise to microscopic diffusion tensors with oblate, spherical, and prolate shapes. The method could be useful for characterizing the geometry of fluid-filled compartments in porous solids, soft matter, and biological tissues.

Detection of Imperceptible Intervertebral Disc Fissures in Conventional MRI-An AI Strategy for Improved Diagnostics.

Annular fissures in the intervertebral discs are believed to be closely related to back pain. However, no sensitive non-invasive method exists to detect annular fissures. This study aimed to propose and test a method capable of detecting the presence and position of annular fissures in conventional magnetic resonance (MR) images non-invasively. The method utilizes textural features calculated from conventional MR images combined with attention mapping and artificial intelligence (AI)-based classification models. As ground truth, reference standard computed tomography (CT) discography was used. One hundred twenty-three intervertebral discs in 43 patients were examined with MR imaging followed by discography and CT. The fissure classification model determined the presence of fissures with 100% sensitivity and 97% specificity. Moreover, the true position of the fissures was correctly determined in 90 (87%) of the analyzed discs. Additionally, the proposed method was significantly more accurate at identifying fissures than the conventional radiological high-intensity zone marker. In conclusion, the findings suggest that the proposed method is a promising diagnostic tool to detect annular fissures of importance for back pain and might aid in clinical practice and allow for new non-invasive research related to the presence and position of individual fissures.

Texture Analysis of Magnetic Resonance Images Enables Phenotyping of Potentially Painful Annular Fissures.

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVE: To investigate whether intervertebral disc (IVD) image features, extracted from magnetic resonance (MR) images, can depict the extension and width of annular fissures and associate them to pain. SUMMARY OF BACKGROUND DATA: Annular fissures are suggested to be associated with low back pain (LBP). Magnetic resonance imaging (MRI) is a sensitive method, yet fissures are sometimes unobservable in T2-weighted MR-images, even though fissure information is present in the image. Image features can mathematically be calculated from MR-images and might reveal fissure characteristics. METHODS: Forty four LBP patients who underwent MRI, low-pressure discography (<50 psi), and computed tomography (CT) sequentially in 1 day, were reviewed. After semi-automated segmentation of 126 discs, image features were extracted from the T2-weighted images. The number of image features was reduced with principle component analysis (PCA). CT-discograms were graded and dichotomized regarding extension and width of fissures. IVDs were divided into fissures extending to outer annulus versus short/no fissures. Fissure width was dichotomized into narrow (<10%) versus broad fissures (>10%), and into moderately broad (10%-50%) versus very broad fissures (>50%). Logistic regression was performed to investigate if image features could depict fissure extension to outer annulus and fissure width. As a sub-analysis, the association between image features used to depict fissure characteristics and discography-provoked pain-response were investigated. RESULTS: Fissure extension could be depicted with sensitivity/specificity = 0.97/0.77 and area under curve (AUC) = 0.97. Corresponding results for width depiction were sensitivity/specificity = 0.94/0.39 and 0.85/0.62, and AUC = 0.86 and 0.81 for narrow versus broad and moderately broad versus very broad fissures respectively. Pain prediction with image features used for depicting fissure characteristics showed sensitivity/specificity = 0.90/0.36, 0.88/0.4, 0.93/0.33; AUC = 0.69, 0.75, and 0.73 respectively. CONCLUSION: Standard MR-images contains fissure information associated to pain that can be depicted with image features, enabling non-invasive phenotyping of potentially painful annular fissures.Level of Evidence: 2.

A Reperfusion BOLD-MRI Tissue Perfusion Protocol Reliably Differentiate Patients with Peripheral Arterial Occlusive Disease from Healthy Controls.

There is no established technique that directly quantifies lower limb tissue perfusion. Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) is an MRI technique that can determine skeletal muscle perfusion. BOLD-MRI relies on magnetic differences of oxygenated and deoxygenated hemoglobin, and regional changes in oxy/deoxyhemoglobin ratio can be recorded by T2* weighted MRI sequences. We aimed to test whether BOLD-MRI can differentiate lower limb tissue perfusion in peripheral arterial occlusive disease (PAOD) patients and healthy controls. Twenty-two PAOD patients and ten healthy elderly volunteers underwent lower limb BOLD-MRI. Reactive hyperemia was provoked by transient cuff compression and images of the gastrocnemius and soleus muscles were continuously acquired at rest, during ischemia and reperfusion. Key BOLD parameters were baseline T2* absolute value and time to T2* peak value after cuff deflation (TTP). Correlations between imaging parameters and ankle-brachial index (ABI) was investigated. The mean TTP was considerably prolonged in PAOD patients compared to healthy controls (m. gastrocnemius: 111 ± 46 versus 48 ± 22 s, p = 0.000253; m. soleus: 100 ± 42 versus 41 ± 30 s, p = 0.000216). Both gastrocnemius and soleus TTP values correlated strongly with ABI (-0.82 and -0.78, p < 0.01). BOLD-MRI during reactive hyperemia differentiated most PAOD patients from healthy controls. TTP was the most decisive parameter and strongly correlated with the ABI.

NMR quantification of diffusional exchange in cell suspensions with relaxation rate differences between intra and extracellular compartments.

Water transport across cell membranes can be measured non-invasively with diffusion NMR. We present a method to quantify the intracellular lifetime of water in cell suspensions with short transverse relaxation times, T2, and also circumvent the confounding effect of different T2 values in the intra- and extracellular compartments. Filter exchange spectroscopy (FEXSY) is specifically sensitive to exchange between compartments with different apparent diffusivities. Our investigation shows that FEXSY could yield significantly biased results if differences in T2 are not accounted for. To mitigate this problem, we propose combining FEXSY with diffusion-relaxation correlation experiment, which can quantify differences in T2 values in compartments with different diffusivities. Our analysis uses a joint constrained fitting of the two datasets and considers the effects of diffusion, relaxation and exchange in both experiments. The method is demonstrated on yeast cells with and without human aquaporins.

Microemulsions of Record Low Amphiphile Concentrations Are Affected by the Ambient Gravitational Field.

It is shown that the ternary system heavy water-heptane-hexadecyl hexaethylene oxide (C16E6) has a stable bicontinuous microemulsion phase down to an exceptionally low concentration at the balanced temperature of 26.8 °C. It is further demonstrated that the ambient gravitational field has an influence on the observed phase equilibria for typical sample sizes (∼1 cm). Direct measurements using a nuclear magnetic resonance imaging technique demonstrate that sample compositions vary with the height in the vials. It is furthermore found that some samples show four phases at equilibrium in apparent violation of Gibbs' phase rule. It is pointed out that Gibbs' phase rule strictly applies only when effects of gravity are negligible. A further consequence of the ambient gravitational field is that, for the system studied, the microemulsion one-phase samples are not observed, when using standard size vials, that is, sample heights on the order of a centimeter. Quantitative determinations of concentration profiles can be used to determine parameters of the free-energy density for the system.

Isotropic diffusion weighting in PGSE NMR by magic-angle spinning of the q-vector.

When PGSE NMR is applied to water in microheterogeneous materials such as liquid crystals, foodstuffs, porous rocks, and biological tissues, the signal attenuation is often multi-exponential, indicating the presence of pores having a range of sizes or anisotropic domains having a spread of orientations. Here we modify the standard PGSE experiment by introducing low-amplitude harmonically modulated gradients, which effectively make the q-vector perform magic-angle spinning (MAS) about an axis fixed in the laboratory frame. With this new technique, denoted q-MAS PGSE, the signal attenuation depends on the isotropic average of the local diffusion tensor. The capability of q-MAS PGSE to distinguish between pore size and domain orientation dispersion is demonstrated by experiments on a yeast cell suspension and a polydomain anisotropic liquid crystal. In the latter case, the broad distribution of apparent diffusivities observed with PGSE is narrowed to its isotropic average with q-MAS PGSE in a manner that is analogous to the narrowing of chemical shift anisotropy powder patterns using magic-angle sample spinning in solid-state NMR. The new q-MAS PGSE technique could be useful for resolving size/orientation ambiguities in the interpretation of PGSE data from, e.g., water confined within the axons of human brain tissue.