Effect of interstitial fluid pressure on shear wave elastography: an experimental and computational study.

Objective. An elevated interstitial fluid pressure (IFP) can lead to strain-induced stiffening of poroelastic biological tissues. As shear wave elastography (SWE) measures functional tissue stiffness based on the propagation speed of acoustically induced shear waves, the shear wave velocity (SWV) can be used as an indirect measurement of the IFP. The underlying biomechanical principle for this stiffening behavior with pressurization is however not well understood, and we therefore studied how IFP affects SWV through SWE experiments and numerical modeling.Approach. For model set-up and verification, SWE experiments were performed while dynamically modulating IFP in a chicken breast. To identify the confounding factors of the SWV-IFP relationship, we manipulated the material model (linear poroelastic versus porohyperelastic), deformation assumptions (geometric linearity versus nonlinearity), and boundary conditions (constrained versus unconstrained) in a finite element model mimicking the SWE experiments.Main results. The experiments demonstrated a statistically significant positive correlation between the SWV and IFP. The model was able to reproduce a similar SWV-IFP relationship by considering an unconstrained porohyperelastic tissue. Material nonlinearity was identified as the primary factor contributing to this relationship, whereas geometric nonlinearity played a smaller role. The experiments also highlighted the importance of the dynamic nature of the pressurization procedure, as indicated by a different observed SWV-IFP for pressure buildup and relaxation, but its clinical relevance needs to be further investigated.Significance. The developed model provides an adaptable framework for SWE of poroelastic tissues and paves the way towards non-invasive measurements of IFP.

Noninvasive Magnetic Resonance Imaging Measures of Glymphatic System Activity.

The comprehension of the glymphatic system, a postulated mechanism responsible for the removal of interstitial solutes within the central nervous system (CNS), has witnessed substantial progress recently. While direct measurement techniques involving fluorescence and contrast agent tracers have demonstrated success in animal studies, their application in humans is invasive and presents challenges. Hence, exploring alternative noninvasive approaches that enable glymphatic research in humans is imperative. This review primarily focuses on several noninvasive magnetic resonance imaging (MRI) techniques, encompassing perivascular space (PVS) imaging, diffusion tensor image analysis along the PVS, arterial spin labeling, chemical exchange saturation transfer, and intravoxel incoherent motion. These methodologies provide valuable insights into the dynamics of interstitial fluid, water permeability across the blood-brain barrier, and cerebrospinal fluid flow within the cerebral parenchyma. Furthermore, the review elucidates the underlying concept and clinical applications of these noninvasive MRI techniques, highlighting their strengths and limitations. It addresses concerns about the relationship between glymphatic system activity and pathological alterations, emphasizing the necessity for further studies to establish correlations between noninvasive MRI measurements and pathological findings. Additionally, the challenges associated with conducting multisite studies, such as variability in MRI systems and acquisition parameters, are addressed, with a suggestion for the use of harmonization methods, such as the combined association test (COMBAT), to enhance standardization and statistical power. Current research gaps and future directions in noninvasive MRI techniques for assessing the glymphatic system are discussed, emphasizing the need for larger sample sizes, harmonization studies, and combined approaches. In conclusion, this review provides invaluable insights into the application of noninvasive MRI methods for monitoring glymphatic system activity in the CNS. It highlights their potential in advancing our understanding of the glymphatic system, facilitating clinical applications, and paving the way for future research endeavors in this field. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.

Non-invasive imaging of interstitial fluid transport parameters in solid tumors in vivo.

In this paper, new and non-invasive imaging methods to assess interstitial fluid transport parameters in tumors in vivo are developed, analyzed and experimentally validated. These parameters include extracellular volume fraction (EVF), interstitial fluid volume fraction (IFVF) and interstitial hydraulic conductivity (IHC), and they are known to have a critical role in cancer progression and drug delivery effectiveness. EVF is defined as the volume of extracellular matrix per unit volume of the tumor, while IFVF refers to the volume of interstitial fluid per unit bulk volume of the tumor. There are currently no established imaging methods to assess interstitial fluid transport parameters in cancers in vivo. We develop and test new theoretical models and imaging techniques to assess fluid transport parameters in cancers using non-invasive ultrasound methods. EVF is estimated via the composite/mixture theory with the tumor being modeled as a biphasic (cellular phase and extracellular phase) composite material. IFVF is estimated by modeling the tumor as a biphasic poroelastic material with fully saturated solid phase. Finally, IHC is estimated from IFVF using the well-known Kozeny-Carman method inspired by soil mechanics theory. The proposed methods are tested using both controlled experiments and in vivo experiments on cancers. The controlled experiments were performed on tissue mimic polyacrylamide samples and validated using scanning electron microscopy (SEM). In vivo applicability of the proposed methods was demonstrated using a breast cancer model implanted in mice. Based on the controlled experimental validation, the proposed methods can estimate interstitial fluid transport parameters with an error below 10% with respect to benchmark SEM data. In vivo results demonstrate that EVF, IFVF and IHC increase in untreated tumors whereas these parameters are observed to decrease over time in treated tumors. The proposed non-invasive imaging methods may provide new and cost-effective diagnostic and prognostic tools to assess clinically relevant fluid transport parameters in cancers in vivo.

An optimized b-value sampling for the quantification of interstitial fluid using diffusion-weighted MRI, a genetic algorithm approach.

PURPOSE: Multi-b-value diffusion-weighted MRI techniques can simultaneously measure the parenchymal diffusivity, microvascular perfusion, and a third, intermediate diffusion component. This component is related to the interstitial fluid in the brain parenchyma. However, simultaneously estimating three diffusion components from multi-b-value data is difficult and has strong dependence on SNR and chosen b-values. As the number of acquired b-values is limited due to scanning time, it is important to know which b-values are most effective to be included. Therefore, this study evaluates an optimized b-value sampling for interstitial fluid estimation. METHOD: The optimized b-value sampling scheme is determined using a genetic algorithm. Subsequently, the performance of this optimized sampling is assessed by comparing it with a linear, logarithmic, and previously proposed sampling scheme, in terms of the RMS error (RMSE) for the intermediate component estimation. The in vivo performance of the optimized sampling is assessed using 7T data with 101 equally spaced b-values ranging from 0 to 1000 s/mm2 . In this case, the RMSE was determined by comparing the fit that includes all b-values. RESULTS: The optimized b-value sampling for estimating the intermediate component was reported to be [0, 30, 90, 210, 280, 350, 580, 620, 660, 680, 720, 760, 980, 990, 1000] s/mm2 . For computer simulations, the optimized sampling had a lower RMSE, compared with the other samplings for varying levels of SNR. For the in vivo data, the voxel-wise RMSE of the optimized sampling was lower compared with other sampling schemes. CONCLUSION: The genetic algorithm-optimized b-value scheme improves the quantification of the diffusion component related to interstitial fluid in terms of a lower RMSE.

Diffusion-weighted image analysis along the perivascular space (DWI-ALPS) for evaluating interstitial fluid status: age dependence in normal subjects.

PURPOSE: The purpose of this study was to evaluate the interstitial fluid status in a wide range of age groups using diffusion-weighted image analysis along the perivascular space (DWI-ALPS) method, which is a simplified variation of diffusion tensor image analysis along the perivascular space (DTI-ALPS). MATERIALS AND METHODS: This retrospective study included data from 128 patients who underwent clinical magnetic resonance imaging (MRI) studies, including DWI, and were found to have no abnormal findings in the brain on MRI. Three motion-probing gradients of the DWI were applied in an orthogonal direction to the imaging plane. Apparent diffusion coefficient images in the x-, y-, and z-axes were retrospectively generated, and composite color images were created to locate the projection and association fiber area on the slice including the body of the lateral ventricle. ALPS indices were calculated, and correlations with age were evaluated using linear and second-degree regression analysis. Linear regression analysis was also performed for a subgroup of patients older than 40 years. In addition, an analysis of variance (ANOVA) test among the generations was performed. RESULTS: The linear regression analysis between age and the ALPS index showed a correlation coefficient of -0.20 for all age group and -0.51 for the subgroup older than 40 years. The second-degree regression analysis showed a correlation coefficient of 0.39. ANOVA showed that the 40's generation showed a statistically significant higher value of ALPS index compared to all other generations except for the 30's generation. While, the 70's generation showed a statistically significant lower value of the ALPS index compared to all other generations. CONCLUSIONS: The analysis of the DWI-APLS method showed a correlation between age and the ALPS index in second-degree distribution which peaked in the 40's generation. This finding in normal subjects may be fundamental in the analysis of disease cases. We tried to evaluate the glymphatic system status in a wide range of age groups using diffusion-weighted image analysis along the perivascular space (DWI-ALPS) method, and the results showed a correlation between age and the ALPS index in second-degree distribution which peaked in the 40's generation.

Current Concepts in Intracranial Interstitial Fluid Transport and the Glymphatic System: Part II-Imaging Techniques and Clinical Applications.

The glymphatic system is a recently discovered network unique to the central nervous system that allows for dynamic exchange of interstitial fluid (ISF) and cerebrospinal fluid (CSF). As detailed in part I, ISF and CSF transport along paravascular channels of the penetrating arteries and possibly veins allow essential clearance of neurotoxic solutes from the interstitium to the CSF efflux pathways. Imaging tests to investigate this neurophysiologic function, although challenging, are being developed and are reviewed herein. These include direct visualization of CSF transport using postcontrast imaging techniques following intravenous or intrathecal administration of contrast material and indirect glymphatic assessment with detection of enlarged perivascular spaces. Application of MRI techniques, including intravoxel incoherent motion, diffusion tensor imaging, and chemical exchange saturation transfer, is also discussed, as are methods for imaging dural lymphatic channels involved with CSF efflux. Subsequently, glymphatic function is considered in the context of proteinopathies associated with neurodegenerative diseases and traumatic brain injury, cytotoxic edema following acute ischemic stroke, and chronic hydrocephalus after subarachnoid hemorrhage. These examples highlight the substantial role of the glymphatic system in neurophysiology and the development of certain neuropathologic abnormalities, stressing the importance of its consideration when interpreting neuroimaging investigations. © RSNA, 2021.

Increased extracellular fluid is associated with white matter fiber degeneration in CADASIL: in vivo evidence from diffusion magnetic resonance imaging.

BACKGROUND: White matter hyperintensities (WMHs) are one of the hallmarks of cerebral small vessel disease (CSVD), but the pathological mechanisms underlying WMHs remain unclear. Recent studies suggest that extracellular fluid (ECF) is increased in brain regions with WMHs. It has been hypothesized that ECF accumulation may have detrimental effects on white matter microstructure. To test this hypothesis, we used cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) as a unique CSVD model to investigate the relationships between ECF and fiber microstructural changes in WMHs. METHODS: Thirty-eight CADASIL patients underwent 3.0 T MRI with multi-model sequences. Parameters of free water (FW) and apparent fiber density (AFD) obtained from diffusion-weighted imaging (b = 0 and 1000 s/mm2) were respectively used to quantify the ECF and fiber density. WMHs were split into four subregions with four levels of FW using quartiles (FWq1 to FWq4) for each participant. We analyzed the relationships between FW and AFD in each subregion of WMHs. Additionally, we tested whether FW of WMHs were associated with other accompanied CSVD imaging markers including lacunes and microbleeds. RESULTS: We found an inverse correlation between FW and AFD in WMHs. Subregions of WMHs with high-level of FW (FWq3 and FWq4) were accompanied with decreased AFD and with changes in FW-corrected diffusion tensor imaging parameters. Furthermore, FW was also independently associated with lacunes and microbleeds. CONCLUSIONS: Our study demonstrated that increased ECF was associated with WM degeneration and the occurrence of lacunes and microbleeds, providing important new insights into the role of ECF in CADASIL pathology. Improving ECF drainage might become a therapeutic strategy in future.

Diffusion-Weighted Magnetic Resonance Imaging as a Noninvasive Parameter for Differentiating Benign and Malignant Intraperitoneal Collections.

Background and Objective: The imaging differentiation of benign from malignant intraperitoneal collections (IPCs) relies on the tumoral morphological modifications of the peritoneum, which are not always advocating for malignancy. We aimed to assess ascitic fluid with the apparent diffusion coefficient (ADC) to determine non-invasive, stand-alone, differentiation criteria for benign and malignant intraperitoneal effusions. Materials and Methods: Sixty-one patients with known IPCs who underwent magnetic resonance examinations for reasons such as tumor staging, undetermined abdominal mass and disease follow up were retrospectively included in this study. All subjects had a final diagnosis of the fluid based on pathological examinations, which were divided into benign (n = 37) and malignant (n = 24) IPCs groups. ADC values were measured separately by two radiologists, and the average values were used for comparing the two groups by consuming the independent samples t-test. The receiver operating characteristic analysis was performed to test the ADC values' diagnostic ability to distinguish malignant from benign collections. Results: The differentiation between benign and malignant IPCs based on ADC values was statistically significant (p = 0.0034). The mean ADC values were higher for the benign (3.543 × 10-3 mm2/s) than for the malignant group (3.057 × 10-3 mm2/s). The optimum ADC cutoff point for the diagnosis of malignant ascites was <3.241 × 10-3 mm2/s, with a sensitivity of 77.78% and a specificity of 80%. Conclusions: ADC represents a noninvasive and reproducible imaging parameter that may help to assess intraperitoneal collections. Although successful in distinguishing malignant from benign IPCs, further research must be conducted in order to certify if the difference in ADC values is a consequence of the physical characteristics of the ascitic fluids or their appurtenance to a certain histopathological group.

Location-specific characteristics of perivascular spaces as the brain's interstitial fluid drainage system.

PURPOSE: Brain interstitial fluid plays an important role in the excretion of metabolic waste products into the cerebrospinal fluid through perivascular spaces (PVS). To investigate the normal function of PVS in healthy elderly individuals, we assessed the relationship between PVS and white matter hyperintensity (WMH) on MRI in two locations. METHODS: This study included 296 healthy individuals aged ≥60 years without a history of brain disease who underwent brain MRI. The severities of PVS and WMH were assessed on the location-specific classification in the basal ganglia (BG-PVS) or centrum semiovale (CSO-PVS), and in the deep or periventricular WMH. RESULTS: The severity of BG-PVS was significantly associated with the severities of deep and periventricular WMHs. In contrast, the severity of CSO-PVS was inversely associated with the severity of deep WMH and was not significantly associated with that of periventricular WMH. The multivariate odds ratios of severe deep WMH for BG-PVS and CSO-PVS were 1.18 (95% CIs: 1.01-1.38) and 0.68 (0.54-0.86), respectively, compared with none deep WMH. CONCLUSIONS: CSO-PVS looks different from BG-PVS in their relationship with deep WMHs. Therefore, CSO-PVS might play an essential role in the normal interstitial fluid drainage system, not as a biomarker of arteriosclerosis.

Fluid signal in the mastoid is a common incidental finding on MRI of the brain.

Incidental findings are common on patients undergoing magnetic resonance imaging (MRI) of the brain. Fluid signal in the mastoid can be such an incidental finding on MRI of the brain. In only a small number of patients, this relates to inflammatory disease of the middle ear or mastoid. In a small retrospective study, the prevalence of this finding has been studied. Fluid signal in the mastoid was found in 21 out of 84 patients (25%). Only in two patients MRI revealed a cause for the mastoid fluid (mastoid osteolysis in a patient with metastatic breast cancer and presumed recurrent cholesteatoma in another patient). Two patients reported about longstanding presbyacusis. At the initial examination, none of the patients reported symptoms of an inflammatory otological disease, and clinical examination was unremarkable in all patients. In conclusion, fluid signal in the mastoid seems to be a frequent incidental finding in asymptomatic patients. A diagnosis of mastoiditis should only be made if there are distinct clinical findings.

Phase contrast MRI of creeping flows using stimulated echo.

Creeping flows govern many important physiological phenomena such as elevated interstitial fluid flows in tumors, glymphatic flows in the brain, among other applications. However, few methods exist to measure such slow flows non-invasively in optically opaque biological tissues in vivo. Phase-contrast MRI is a velocimetry technique routinely used in the clinic to measure fast flows in biological tissues, such as blood and cerebrospinal fluid (CSF), in the order of cm/s. Use of this technique to encode slower flows is hampered by diffusion weighting and phase error introduced by gradient hardware imperfections. In this study, a new PC-MRI technique is developed using stimulated echo preparation to overcome these challenges. Flows as slow as 1 µm/s are measured and validated using controlled water flow through a pipe at 4.7 T. The error in measured flow rate obtained by integrating the measured velocity over the cross-sectional area of the pipe is less than 10%. The developed method was also able to capture slow natural convection flows appearing in liquids placed inside a horizontal bore magnet. Monitoring the 4D velocity vector field revealed that the natural convection flows decay exponentially with time. This method could be applied in future to study creeping flows, e.g. in tissue.

Normative Interlimb Impedance Ratios: Implications for Early Diagnosis of Uni- and Bilateral, Upper and Lower Limb Lymphedema.

Background: Bioimpedance spectroscopy detects unilateral lymphedema if the ratio of extracellular fluid (ECF) between arms or between legs is outside three standard deviations (SDs) of the normative mean. Detection of bilateral lymphedema, common after bilateral breast or gynecological cancer, is complicated by the unavailability of an unaffected contralateral limb. The objectives of this work were to (1) present normative values for interarm, interleg, and arm-to-leg impedance ratios of ECF and ECF normalized to intracellular fluid (ECF/ICF); (2) evaluate the influence of sex, age, and body mass index on ratios; and (3) describe the normal change in ratios within healthy individuals over time. Methods: Data from five studies were combined to generate a normative data set (n = 808) from which mean and SD were calculated for interarm, interleg, and arm-to-leg ratios of ECF and ECF/ICF. The influence of sex, age, and body mass index was evaluated using multiple linear regression, and normative change was calculated for participants with repeated measures by subtracting their lowest ratio from their highest ratio. Results: Mean (SD) interarm, interleg, dominant arm-to-leg, and nondominant arm-to-leg ratios were 0.987 (0.067), 1.005 (0.072), 1.129 (0.160), and 1.165 (0.174) for ECF ratios; and 0.957 (0.188), 1.024 (0.183), 1.194 (0.453), and 1.117 (0.367) for ECF/ICF ratios, respectively. Arm-to-leg ratios were significantly affected by sex, age, and body mass index. Mean normative change ranged from 7.2% to 14.7% for ECF ratios and from 14.7% to 67.1% for ECF/ICF ratios. Conclusion: These findings provide the necessary platform for extending bioimpedance-based screening beyond unilateral lymphedema.

A model-based approach to investigate the effect of elevated interstitial fluid pressure on strain elastography.

Finite element (FE) modeling provides a useful tool to understand the mechanical behavior of complex tissues, such as cancers, in a variety of testing conditions. Although a number of numerical and analytical models for cancerous tumors are retrievable in the literature, none of these models is capable of completely describing the behavior of a cancer embedded in a normal tissue in the conditions typical for an ultrasound elastography experiment. In this paper, we first design and implement a realistic FE model of the mechanical behavior of a cancer embedded in a normal tissue under ultrasound elastography testing conditions. In addition to the commonly used tissue mechanical properties, for the cancer, elevated interstitial fluid pressure (IFP) is incorporated in the model. IFP is a parameter of great clinical significance, but it is not typically considered in elastographic models of tumors. The developed model is then used to thoroughly study the effect of IFP on the axial, lateral and volumetric strains inside the tumor. The results of this study demonstrate that the presence of the IFP affects both the temporal and spatial distributions of the axial, lateral, volumetric strains and related elastographic parameters. Thus, these results lead to two important considerations: (1) that a correct interpretation of experimental elastographic data need a clear understanding of the effect of the IFP on the obtained elastograms and (2) that this IFP-dependent alteration of the elastographic parameters may provide an opportunity to non-invasively gain localized information about this clinically relevant parameter.

Usefulness of new subtraction algorithm in estimating degree of liver fibrosis by calculating extracellular volume fraction obtained from routine liver CT protocol equilibrium phase data: Preliminary experience.

OBJECTIVES: To assess whether extracellular volume fraction (ECV) obtained from routine liver CT equilibrium phase data utilizing new subtraction algorithm is useful in estimating the degree of liver fibrosis. MATERIALS AND METHODS: Consecutive 41 patients, 21 men and 20 women, with chronic liver diseases who underwent quadri-phase liver CT and MR elastography within 3 months were retrospectively enrolled. Subtraction image of unenhanced from equilibrium phase (240 s) images using conventional and new algorithms were made. We firstly assessed the quality of these subtraction algorithms using patients in whom anatomical misregistration between the two image sets were prominent. Then, ECVs were calculated using both subtraction data sets (ECV-convSub, and ECV-newSub, respectively). ECV were also calculated by traditional manual method (ECV-man). Correlation coefficients of 3 types of ECV were compared using liver stiffness (kPa) as measured by MR elastography and pathologically proven fibrosis grades as reference standards. RESULTS: For eleven patients with prominent anatomical misregistration between the unenhanced and equilibrium phases, new algorithm provided significantly better subtraction images than the conventional one (p = 0.001, Wilcoxon's signed rank test). As for correlation with liver stiffness, R2 for ECV-man, ECV-convSub, and ECV-newSub, were 0.57, 0.59, and 0.66, respectively (all p < 0.0001, Pearson's correlation). Histological assessment for fibrosis grades were available in 20 patients, and rho values for these three ECVs were 0.66, 0.61, and 0.71, respectively (all p < 0.01, Spearman's rank correlation). CONCLUSION: ECV-newSub showed better correlation to liver stiffness and pathological fibrosis grades than ECV-convSub and ECV-man, which could be a reliable biomarker of liver fibrosis obtained from routine clinical diagnostic imaging data, where equilibrium phase delay time was set at 240 s.

Toward a noninvasive estimate of interstitial fluid pressure by dynamic contrast-enhanced MRI in a rat model of cerebral tumor.

PURPOSE: This study demonstrates a DCE-MRI estimate of tumor interstitial fluid pressure (TIFP) and hydraulic conductivity in a rat model of glioblastoma, with validation against an invasive wick-in-needle (WIN) technique. An elevated TIFP is considered a mark of aggressiveness, and a decreased TIFP a predictor of response to therapy. METHODS: The DCE-MRI studies were conducted in 36 athymic rats (controls and posttreatment animals) with implanted U251 cerebral tumors, and with TIFP measured using a WIN method. Using a model selection paradigm and a novel application of Patlak and Logan plots to DCE-MRI data, the MRI parameters required for estimating TIFP noninvasively were estimated. Two models, a fluid-mechanical model and a multivariate empirical model, were used for estimating TIFP, as verified against WIN-TIFP. RESULTS: Using DCE-MRI, the mean estimated hydraulic conductivity (MRI-K) in U251 tumors was (2.3 ± 3.1) × 10-5 (mm2 /mmHg-s) in control studies. Significant positive correlations were found between WIN-TIFP and MRI-TIFP in both mechanical and empirical models. For instance, in the control group of the fluid-mechanical model, MRI-TIFP was a strong predictor of WIN-TIFP (R2 = 0.76, p < .0001). A similar result was found in the bevacizumab-treated group of the empirical model (R2 = 0.93, p = .014). CONCLUSION: This research suggests that MRI dynamic studies contain enough information to noninvasively estimate TIFP in this, and possibly other, tumor models, and thus might be used to assess tumor aggressiveness and response to therapy.

Aquaporin-4 facilitator TGN-073 promotes interstitial fluid circulation within the blood-brain barrier: [17O]H2O JJVCPE MRI study.

The blood-brain barrier (BBB), which imposes significant water permeability restriction, effectively isolates the brain from the systemic circulation. Seemingly paradoxical, the abundance of aquaporin-4 (AQP-4) on the inside of the BBB strongly indicates the presence of unique water dynamics essential for brain function. On the basis of the highly specific localization of AQP-4, namely, astrocyte end feet at the glia limitans externa and pericapillary Virchow-Robin space, we hypothesized that the AQP-4 system serves as an interstitial fluid circulator, moving interstitial fluid from the glia limitans externa to pericapillary Virchow-Robin space to ensure proper glymphatic flow draining into the cerebrospinal fluid. The hypothesis was tested directly using the AQP-4 facilitator TGN-073 developed in our laboratory, and [O]H2O JJ vicinal coupling proton exchange MRI, a method capable of tracing water molecules delivered into the blood circulation. The results unambiguously showed that facilitation of AQP-4 by TGN-073 increased turnover of interstitial fluid through the system, resulting in a significant reduction in [O]H2O contents of cortex with normal flux into the cerebrospinal fluid. The study further suggested that in addition to providing the necessary water for proper glymphatic flow, the AQP-4 system produces a water gradient within the interstitial space promoting circulation of interstitial fluid within the BBB.

Breast Cancer-Related Lymphedema: Differentiating Fat from Fluid Using Magnetic Resonance Imaging Segmentation.

BACKGROUND: Lymphedema is an iatrogenic complication after breast cancer treatment in which lymph fluid in the affected limb progresses to fat deposition and fibrosis that are amenable to liposuction treatment. Magnetic resonance imaging (MRI) for lymphedema can differentiate fat tissue from fluid, but estimating relative volumes remains problematic. METHODS AND RESULTS: Patients underwent routine bilateral arm MRI both before and after liposuction for advanced lymphedema. The threshold-based level set (TLS) segmentation method was applied to segment the geometric image data and to measure volumes of soft tissue (fat, muscle, and lymph fluid) and bone. Bioimpedance testing (L-Dex®) to detect extracellular fluid was also used. Volumes derived by using TLS or girth measurement were evaluated and showed consistent agreement, whereas L-Dex showed no significant reduction between pre- and postoperative measures. The percentage median volume difference between the affected and unaffected sides was 132.4% for girth measures compared with 137.2% for TLS (p = 0.175) preoperatively, and 99.8% and 98.5%, respectively (p = 0.600), postoperatively. MRI segmentation detected reductions in fat (median 52.6%, p = 0.0163) and lymph fluid (median 66%, p = 0.094), but the volumes of muscle and bone were relatively constant. CONCLUSIONS: MRI imaging with TLS technology may be a useful tool to quantitatively measure fat tissue and fluid for patients with advanced lymphedema and may assist in the selection of eligible liposuction candidates at initial assessment and follow-up of patients who proceed with surgery.

Acute changes in extracellular volume fraction in skeletal muscle monitored by 23Na NMR spectroscopy.

In this article, we induced acute changes in extracellular volume fraction in skeletal muscle tissue and compared the sensitivity of a standard 1H T2 imaging method with different 23Na-NMR spectroscopy parameters within acquisition times compatible with clinical investigations. First, we analyzed the effect of a short ischemia on the sodium distribution in the skeletal muscle. Then, the lower leg of 21 healthy volunteers was scanned under different vascular filling conditions (vascular draining, filling, and normal condition) expected to modify exclusively the extracellular volume. The first experiment showed no change in the total sodium content during a 15 min ischemia, but the intracellular weighted 23Na signal slowly decreased. For the second part, significant variations of total sodium content, sodium distribution, and T1 and T2∗ of 23Na signal were observed between different vascular filling conditions. The measured sodium distribution correlates significantly with sodium T1 and with the short and long T2∗ fractions. In contrast, significant changes in the proton T2w signal were observed only in three muscles. Altogether, the mean T2w signal intensity of all muscles as well as their mean T2 did not vary significantly with the extracellular volume changes. In conclusion, at the expense of giving up spatial resolution, the proposed 23Na spectroscopic method proved to be more sensitive than standard 1H T2 approach to monitor acute extracellular compartment changes within muscle tissue.