Simple compensation method for improved half-pulse excitation profile with rephasing gradient.

PURPOSE: To improve the slice profile quality obtained by RF half-pulse excitation for 2D-UTE applications. METHODS: The overall first-order and zero-order phase errors along the slice-selection direction were obtained with the help of an optimization task to minimize the out-of-slice signal contamination from the calibration 1-dimenisonal (1D) profile data. The time-phase-error evolution was approximated from the k-space readout data, which were acquired primarily for correction of the readout trajectories during data regridding to the rectilinear grids. The correction of the slice profile was achieved by rephasing gradient pulses applied immediately after the end of excitation. The total prescan calibration typically took less than 2 minutes. RESULTS: The improved image quality using the proposed calibration method was demonstrated both on phantoms and on ankle images obtained from healthy volunteers. It was demonstrated that calibration can be performed either as a separate water phantom measurement or directly as a prescan procedure. CONCLUSION: The slice-profile distortion from the half-pulse excitation could substantially affect the overall fidelity of 2D-UTE images. The presented experiments proved that the image quality could be substantially increased by application of the proposed slice-correction method.

A high duty-cycle, multi-channel, power amplifier for high-resolution radiofrequency encoded magnetic resonance imaging.

OBJECTIVE: A radiofrequency (RF) power amplifier is an essential component of any magnetic resonance imaging (MRI) system. Unfortunately, no commercial amplifier exists to fulfill the needs of the transmit array spatial encoding (TRASE) MRI technique, requiring high duty cycle, high RF output power and independently controlled multi-channel capability. Thus, an RF amplifier for TRASE MRI is needed. MATERIALS AND METHODS: A dual-channel RF power amplifier dedicated for TRASE at 0.22 T (9.27 MHz) was designed and constructed using commercially available components. The amplifier was tested on the bench and used a 0.22 T MRI system with a twisted solenoid and saddle RF coil combination capable of a single-axis TRASE. RESULTS: The amplifier is capable of sequential, dual-channel operation up to 50% duty cycle, 1 kW peak output and highly stable 100 µs RF pulse trains. High spatial resolution one-dimensional TRASE was obtained with the power amplifier to demonstrate its capability. CONCLUSION: The constructed amplifier is the first prototype that meets the requirements of TRASE rectifying limitations of duty cycle and timing presented by commercial RF amplifiers. The amplifier makes possible future high resolution in vivo TRASE MRI.

Site-specific conjugation of the quencher on peptide's N-terminal for the synthesis of a targeted non-spreading activatable optical probe.

Optical imaging offers high sensitivity and portability at low cost. The design of 'smart' or 'activatable' probes can decrease the background noise and increase the specificity of the signal. By conjugating a fluorescent dye and a compatible quencher on each side of an enzyme's substrate, the signal remains in its 'off ' state until it reaches the area where a specific enzyme is expressed. However, the signal can leak from that area unless the dye is attached to a molecule able to bind to a specific target also presented in that area. The aim of this study was to (i) specifically conjugate the quencher on the α-amino group of the peptide's N-terminus, (ii) conjugate the dye on the ε-amino group of a lysine in C-terminus, and (iii) conjugate the carboxyl group of the peptide's C-terminus to an amino group present on an antibody, using carbodiimide chemistry. The use of protecting groups, such as Boc or Fmoc, to allow site-specific conjugation, presents several drawbacks including 'on beads labeling', additional steps required for deprotection and removal from the resin, decreased yield, and dye degradation. A method of preferential labeling of α-amino N-terminal group in slightly acidic solution, proposed by Selo et al. (1996) has partially solved the problem. The present study reports improvements of the method allowing to (i) avoid the homo-bilabeling, (ii) increase the yield of the N-terminal labeling by two folds, and (iii) decrease the cost by 44-fold. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

MRI-based assessment of liver perfusion and hepatocyte injury in the murine model of acute hepatitis.

OBJECTIVE: To assess alterations in perfusion and liver function in the concanavalin A (ConA)-induced mouse model of acute liver failure (ALF) using two magnetic resonance imaging (MRI)-based methods: dynamic contrast-enhanced MRI (DCE-MRI) with Gd-EOB-DTPA contrast agent and arterial spin labelling (ASL). MATERIALS AND METHODS: BALB/c mice were studied using a 9.4 T MRI system. The IntraGateFLASHTM and FAIR-EPI pulse sequences were used for optimum mouse abdomen imaging. RESULTS: The average perfusion values for the liver of the control and ConA group were equal to 245 ± 20 and 200 ± 32 ml/min/100 g (p = 0.008, respectively). DCE-MRI showed that the time to the peak of the image enhancement was 6.14 ± 1.07 min and 9.72 ± 1.69 min in the control and ConA group (p < 0.001, respectively), while the rate of the contrast wash-out in the control and ConA group was 0.037 ± 0.008 and 0.021 ± 0.008 min-1 (p = 0.004, respectively). These results were consistent with hepatocyte injury in the ConA-treated mice as confirmed by histopathological staining. CONCLUSIONS: Both the ASL and DCE-MRI techniques represent a reliable methodology to assess alterations in liver perfusion and hepatocyte integrity in murine hepatitis.

Lactate storm marks cerebral metabolism following brain trauma.

Brain metabolism is thought to be maintained by neuronal-glial metabolic coupling. Glia take up glutamate from the synaptic cleft for conversion into glutamine, triggering glial glycolysis and lactate production. This lactate is shuttled into neurons and further metabolized. The origin and role of lactate in severe traumatic brain injury (TBI) remains controversial. Using a modified weight drop model of severe TBI and magnetic resonance (MR) spectroscopy with infusion of (13)C-labeled glucose, lactate, and acetate, the present study investigated the possibility that neuronal-glial metabolism is uncoupled following severe TBI. Histopathology of the model showed severe brain injury with subarachnoid and hemorrhage together with glial cell activation and positive staining for Tau at 90 min post-trauma. High resolution MR spectroscopy of brain metabolites revealed significant labeling of lactate at C-3 and C-2 irrespective of the infused substrates. Increased (13)C-labeled lactate in all study groups in the absence of ischemia implied activated astrocytic glycolysis and production of lactate with failure of neuronal uptake (i.e. a loss of glial sensing for glutamate). The early increase in extracellular lactate in severe TBI with the injured neurons rendered unable to pick it up probably contributes to a rapid progression toward irreversible injury and pan-necrosis. Hence, a method to detect and scavenge the excess extracellular lactate on site or early following severe TBI may be a potential primary therapeutic measure.

Symmetry of the fornix using diffusion tensor imaging.

PURPOSE: To: 1) Present fornix tractography in its entirety for 20 healthy individuals to assess variability. 2) Provide individual and groupwise whole tract diffusion parameter symmetry assessments prior to clinical application. 3) Compare whole tract diffusion parameter assessments with tract-based spatial statistics (TBSS). MATERIALS AND METHODS: Diffusion tensor imaging (DTI) data were acquired on a 3T Siemens magnetic resonance imaging (MRI) system using a single-shot spin echo planar imaging (EPI) sequence. Individual fornix tractography was conducted and whole tract diffusion parameter symmetries assessed. Whole tract results were compared with asymmetry contrasts conducted with voxelwise statistical analysis of diffusion parameters using TBSS. RESULTS: The fornix tract could be visualized in its entirety including the columns, body, crura, and fimbria. Contrary to the crus and body, there were some tractography inconsistencies of the columns and fimbria across subjects. Although whole tract diffusion parameter asymmetries were nonsignificant, fractional anisotropy (FA) values bordered on statistical significance (P = 0.052). Using TBSS, significant FA asymmetries were identified (P ≤ 0.01, corrected). CONCLUSION: The findings demonstrate consistency of fornix tractography as well as some variability in the columns and fimbria. While parametric assessment demonstrates diffusion parameter symmetry, permutation-based TBSS analysis reveals significant FA asymmetries in the crura and fimbriae.

Magnetic resonance microscopy for assessment of morphological changes in hydrating hydroxypropylmethylcellulose matrix tablets in situ-is it possible to detect phenomena related to drug dissolution within the hydrated matrices?

PURPOSE: So far, the hydrated part of the HPMC matrix has commonly been denoted as a "gel" or "pseudogel" layer. No MRI-based results have been published regarding observation of internal phenomena related to drug dissolution inside swelling polymeric matrices during hydration. The purpose of the study was to detect such phenomena. METHODS: Multiparametric, spatially and temporally resolved T2 MR relaxometry, in situ, was applied to study formation of the hydration progress in HPMC matrix tablets loaded with L-dopa and ketoprofen using a 11.7 T MRI system. Two spin-echo based pulse sequences were used, one of them specifically designed to study short T2 signals. RESULTS: Two components in the T2 decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T2 values, were obtained. Based on the data, different region formation patterns (i.e. multilayer structure) were registered depending on drug presence and solubility. Inside the matrix with incorporated sparingly soluble drug a specific layer formation due to drug dissolution was detected, whereas a matrix with very slightly soluble drug does not form distinct external "gel-like" layer. CONCLUSIONS: We have introduced a new paradigm in the characterization of hydrating matrices using (1)H MRI methods. It reflects molecular mobility and concentration of water inside the hydrated matrix. For the first time, drug dissolution related phenomena, i.e. particular front and region formation, were observed by MRI methods.

1H Spin-Lattice Relaxation Processes in Solutions of H2N-Fe3O4 Nanoparticles: Insights from NMR Relaxometry.

1H spin-lattice relaxation experiments have been performed for water and glycerol/water solutions of H2N-Fe3O4 superparamagnetic nanoparticles (NPs) of about 7 nm diameter. The experiments encompass a broad frequency range covering 3 orders of magnitude, from 10 kHz to 10 MHz (referring to 1H resonance frequency), and have been performed in the temperature range from 298 to 313 K, varying the concentration of the superparamagnetic species. This extensive dataset has been used for twofold purposes. The first one is to serve as a challenge for thorough tests of theoretical models describing nuclear relaxation in solutions of superparamagnetic NPs, depending on their magnetic properties and dynamics of the solvent molecules. The challenge is posed by the wish to reproduce the data in a broad range of magnetic fields (not only at high fields) and by the need to explain the differences in the relaxation scenarios for water and glycerol/water solutions by varying only the solvent parameters. The second purpose is to get insights into the magnetic properties (electronic relaxation properties) of the nanoparticles due to their high applicational potential.

X-ray-Sensitive Doped CaF2-Based MRI Contrast Agents for Local Radiation Dose Measurement.

Ionizing radiation has become widely used in medicine, with application in diagnostic techniques, such as computed tomography (CT) and radiation therapy (RT), where X-rays are used to diagnose and treat tumors. The X-rays used in CT and, in particular, in RT can have harmful side effects; hence, an accurate determination of the delivered radiation dose is of utmost importance to minimize any damage to healthy tissues. For this, medical specialists mostly rely on theoretical predictions of the delivered dose or external measurements of the dose. To extend the practical use of ionizing radiation-based medical techniques, such as magnetic resonance imaging (MRI)-guided RT, a more precise measurement of the internal radiation dose internally is required. In this work, a novel approach is presented to measure dose in liquids for potential future in vivo applications. The strategy relies on MRI contrast agents (CAs) that provide a dose-sensitive signal. The demonstrated materials are (citrate-capped) CaF2 nanoparticles (NPs) doped with Eu3+ or Fe2+/Fe3+ ions. Free electrons generated by ionizing radiation allow the reduction of Eu3+, which produces a very small contrast in MRI, to Eu2+, which induces a strong contrast. Oxidative species generated by high-energy X-rays can be measured indirectly using Fe2+ because it oxidizes to Fe3+, increasing the contrast in MRI. Notably, in the results, a strong increase in the proton relaxation rates is observed for the Eu3+-doped NPs at 40 kV. At 6 MV, a significant increase in proton relaxation rates is observed using CaF2 NPs doped with Fe2+/Fe3+ after irradiation. The presented concept shows great promise for use in the clinic to measure in vivo local ionizing radiation dose, as these CAs can be intravenously injected in a saline solution.

High-resolution MRI encoding using radiofrequency phase gradients.

Although MRI offers highly diagnostic medical imagery, patient access to this modality worldwide is very limited when compared with X-ray or ultrasound. One reason for this is the expense and complexity of the equipment used to generate the switched magnetic fields necessary for MRI encoding. These field gradients are also responsible for intense acoustic noise and have the potential to induce nerve stimulation. We present results with a new MRI encoding principle which operates entirely without the use of conventional B0 field gradients. This new approach--'Transmit Array Spatial Encoding' (TRASE)--uses only the resonant radiofrequency (RF) field to produce Fourier spatial encoding equivalent to conventional MRI. k-space traversal (image encoding) is achieved by spin refocusing with phase gradient transmit fields in spin echo trains. A transmit coil array, driven by just a single transmitter channel, was constructed to produce four phase gradient fields, which allows the encoding of two orthogonal spatial axes. High-resolution two-dimensional-encoded in vivo MR images of hand and wrist were obtained at 0.2 T. TRASE exploits RF field phase gradients, and offers the possibility of very low-cost diagnostics and novel experiments exploiting unique capabilities, such as imaging without disturbance of the main B0 magnetic field. Lower field imaging (<1 T) and micro-imaging are favorable application domains as, in both cases, it is technically easier to achieve the short RF pulses desirable for long echo trains, and also to limit RF power deposition. As TRASE is simply an alternative mechanism (and technology) of moving through k space, there are many close analogies between it and conventional B0 -encoded techniques. TRASE is compatible with both B0 gradient encoding and parallel imaging, and so hybrid sequences containing all three spatial encoding approaches are possible.

Functional MRI of the thoracic spinal cord during vibration sensation.

PURPOSE: To demonstrate that it is possible to acquire accurate functional magnetic resonance images from thoracic spinal cord neurons. MATERIALS AND METHODS: The lower thoracic spinal dermatomes (T7-T11) on the right side of the body were mechanically stimulated by vibration for 15 participants. Neuronal responses to vibration sensation were measured in the thoracic spinal cord using a HASTE sequence on a 3 Tesla MRI system. RESULTS: Signal increases were observed in the corresponding lower thoracic spinal cord segments ipsilateral to the side of stimulation in the dorsal aspect of the spinal cord. CONCLUSION: This is the first study to provide proof of principle that functional imaging of the entire thoracic spinal cord is possible, by detecting neuronal activity in the thoracic spinal cord during sensory stimulation using spinal fMRI.

Optimal dye-quencher pairs for the design of an "activatable" nanoprobe for optical imaging.

Optical imaging offers high sensitivity and portability at low cost. The design of an optimal "activatable" imaging agent could greatly decrease the background noise and increase specificity of the signal. Five different molecules have been used to quench basal fluorescence of an enzyme substrate labeled with Cy5, Cy5.5 or IR800 at a distance of 8 amino acids (32 Å): a 6 nm gold nanoparticle (NP), a 20 nm and a 30 nm iron oxide (FeO) NP, the black hole quencher BHQ-3 and the IRdye quencher QC-1. The quenching efficiencies were 99% for QC1-IR800, 98% for QC1-Cy5.5, 96% for 30 nm FeO NP-Cy5.5, 89% for BHQ3-Cy5, 84% for BHQ3-Cy5.5, 77-90% for 6 nm gold NP-Cy5.5, depending on the number of dyes around the NP, 79% for 20 nm FeO NP-Cy5.5 and 77% for Cy5.5-Cy5. Signal activation upon cleavage by the matrix metalloproteinase MMP9 was proportional to the quenching efficiencies, ranging from 3-fold with Cy5.5-Cy5 to 67-fold with QC1-IR800. This independent work reports on the properties of the dyes and quenchers explaining the superior performance of QC-1 and 30 nm FeO NPs.

Alterations in glycopeptides associated with herceptin treatment of human breast carcinoma mcf-7 and T-lymphoblastoid cells.

The therapeutic humanized monoclonal antibody IgG1 known as Herceptin® has shown remarkable antitumor effects. Although this type of therapy has increased the cancer-free survival of patients, not all tumors respond to this treatment and cancers often develop resistance to the antibody. Despite the fact that Herceptin function has been extensively studied, the precise mechanism underlying its antitumor activity still remains incompletely defined. We previously demonstrated on human breast MCF-7 carcinoma and T-lymphoblastoid CEM cells that monoclonal antibody in combination with Lipoplex consisting of Lipofectamine mixed with plasmid DNA showed a more profound effect on cancer cell viability than antibody alone. The analyses of N-glycans isolated from cancer cells showed dramatic differences in profiles when cells were exposed to Herceptin. Moreover, the investigation of glycosylated peptides from the same cancer cell models after treatment revealed further alterations in the post-translational modifications. Tandem mass spectra obtained from the samples treated confirmed the presence of a series of glycopeptides bearing characteristic oligosaccharides as described in IgG1. However some of them differed by mass differences that corresponded to peptide backbones not described previously and more of them were detected from Herceptin treated samples than from cells transfected with Heceptin/Lipoplex. The results indicate that the presence of Lipoplex prevents antibody transformation and elongates its proper function. The better understanding of the multipart changes described in the glycoconjugates could provide new insights into the mechanism by which antibody induces regression in cancers.

Comparison of T2 and T2*-weighted MR molecular imaging of a mouse model of glioma.

BACKGROUND: Standard MRI has been used for high-grade gliomas detection, albeit with limited success as it does not provide sufficient specificity and sensitivity to detect complex tumor structure. Therefore targeted contrast agents based on iron oxide, that shorten mostly T2 relaxation time, have been recently applied. However pulse sequences for molecular imaging in animal models of gliomas have not been yet fully studied. The aim of this study was therefore to compare contrast-to-noise ratio (CNR) and explain its origin using spin-echo (SE), gradient echo (GE), GE with flow compensation (GEFC) as well as susceptibility weighted imaging (SWI) in T2 and T2* contrast-enhanced molecular MRI of glioma. METHODS: A mouse model was used. U87MGdEGFRvIII cells (U87MG), derived from a human tumor, were injected intracerebrally. A 9.4 T MRI system was used and MR imaging was performed on the 10 day after the inoculation of the tumor. The CNR was measured prior, 20 min, 2 hrs and 24 hrs post intravenous tail administration of glioma targeted paramagnetic nanoparticles (NPs) using SE, SWI, GE and GEFC pulse sequences. RESULTS: The results showed significant differences in CNR among all pulse sequences prior injection. GEFC provided higher CNR post contrast agent injection when compared to GE and SE. Post injection CNR was the highest with SWI and significantly different from any other pulse sequence. CONCLUSIONS: Molecular MR imaging using targeted contrast agents can enhance the detection of glioma cells at 9.4 T if the optimal pulse sequence is used. Hence, the use of flow compensated pulse sequences, beside SWI, should to be considered in the molecular imaging studies.

A truncated twisted solenoid RF phase gradient transmit coil for TRASE MRI.

Transmit array spatial encoding (TRASE) is an MR imaging technique that achieves k-space encoding through the use of phase gradients in the RF transmit field. Without requiring B0 gradient fields, TRASE MRI can be performed using significantly cheaper bi-planar permanent magnets or Halbach arrays. For TRASE encoding with these magnets, the twisted solenoid has been demonstrated as the most efficient RF transmit coil; however, this specific geometry results in a long coil with a relatively short imaging volume. We introduce a new truncated design to increase the usable imaging volume relative to the coil length. Based on simulations of optimal parameters, a 200 mm long, 100 mm inner diameter coil pair was constructed with an imaging volume 100 mm in length and 80 mm in diameter. The coil pair was tested using an un-shimmed 2.84 MHz Halbach array. Results indicate the truncated design can create a similar imaging volume and quality to the untruncated version whilst significantly reducing the length of the coil by as much as a half.

Contrast Enhancement in MRI Using Combined Double Action Contrast Agents and Image Post-Processing in the Breast Cancer Model.

Gd- and Fe-based contrast agents reduce T1 and T2 relaxation times, respectively, are frequently used in MRI, providing improved cancer detection. Recently, contrast agents changing both T1/T2 times, based on core/shell nanoparticles, have been introduced. Although advantages of the T1/T2 agents were shown, MR image contrast of cancerous versus normal adjacent tissue induced by these agents has not yet been analyzed in detail as authors considered changes in cancer MR signal or signal-to-noise ratio after contrast injection rather than changes in signal differences between cancer and normal adjacent tissue. Furthermore, the potential advantages of T1/T2 contrast agents using image manipulation such as subtraction or addition have not been yet discussed in detail. Therefore, we performed theoretical calculations of MR signal in a tumor model using T1-weighted, T2-weighted, and combined images for T1-, T2-, and T1/T2-targeted contrast agents. The results from the tumor model are followed by in vivo experiments using core/shell NaDyF4/NaGdF4 nanoparticles as T1/T2 non-targeted contrast agent in the animal model of triple negative breast cancer. The results show that subtraction of T2-weighted from T1-weighted MR images provides additional increase in the tumor contrast: over two-fold in the tumor model and 12% in the in vivo experiment.

Fe3O4 Magnetic Nanoparticles Obtained by the Novel Aerosol-Based Technique for Theranostic Applications.

This work is aimed at presenting a novel aerosol-based technique for the synthesis of magnetite nanoparticles (Fe3O4 NPs) and to assess the potential medical application of their dispersions after being coated with TEA-oleate. Refinement of the processing conditions led to the formation of monodispersed NPs with average sizes of ∼5-6 nm and narrow size distribution (FWHM of ∼3 nm). The NPs were coated with Triethanolammonium oleate (TEA-oleate) to stabilize them in water dispersion. This allowed obtaining the dispersion, which does not sediment for months, although TEM and DLS studies have shown the formation of small agglomerates of NPs. The different behaviors of cancer and normal cell lines in contact with NPs indicated the diverse mechanisms of their interactions with Fe3O4 NPs. Furthermore, the studies allowed assessment of the prospective theranostic application of magnetite NPs obtained using the aerosol-based technique, particularly magnetic hyperthermia and magnetic resonance imaging (MRI).

Magnetic resonance microscopy for assessment of morphological changes in hydrating hydroxypropylmethyl cellulose matrix tablets in situ.

PURPOSE: To resolve contradictions found in morphology of hydrating hydroxypropylmethyl cellulose (HPMC) matrix as studied using Magnetic Resonance Imaging (MRI) techniques. Until now, two approaches were used in the literature: either two or three regions that differ in physicochemical properties were identified. METHODS: Multiparametric, spatially and temporally resolved T(2) MR relaxometry in situ was applied to study the hydration progress in HPMC matrix tablets using a 11.7 T MRI system. Two spin-echo based pulse sequences-one of them designed to specifically study short T(2) signals-were used. RESULTS: Two components in the T(2) decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T(2) values, were obtained. Based on the data, five different regions and their temporal evolution were identified: dry glassy, hydrated solid like, two interface layers and gel layer. The regions were found to be separated by four evolving fronts identified as penetration, full hydration, total gelification and apparent erosion. CONCLUSIONS: The MRI results showed morphological details of the hydrating HPMC matrices matching compound theoretical models. The proposed method will allow for adequate evaluation of controlled release polymeric matrix systems loaded with drug substances of different solubility.

Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies.

Stereotactic biopsies represent a routine neurosurgical procedure for the diagnosis of intracranial lymphomas and selected diffusely infiltrating gliomas. Acquisition of tissue samples that do not allow correct tumor typing and grading is, however, not uncommon. Five-aminolevulinic acid (5-ALA) has been shown to accumulate in malignant tumor tissue. The aim of this study was to prospectively investigate the clinical usability of 5-ALA for intraoperative detection of representative tissue in stereotactic tumor biopsies. Fifty consecutive patients underwent frameless stereotactic biopsy for a suspected brain tumor. 5-ALA was administered 4 h before anesthesia. Serial biopsy samples were obtained and intraoperatively checked for 5-ALA fluorescence (strong, vague, or none) using a modified neurosurgical microscope. All samples were examined for the presence of representative tumor tissue according to neuroimaging (MRI, positron emission tomography, and/or chemical shift imaging) and histopathological parameters. Visible 5-ALA fluorescence was observed in 43/50 patients (strong in 39 and vague fluorescence in four cases). At biopsy target, 52/53 samples of glioblastomas, 9/10 samples of gliomas grade III, and 14/16 samples of lymphomas revealed strong 5-ALA fluorescence. Samples with strong 5-ALA fluorescence were only observed at, but not outside the biopsy target. All tissue samples with strong 5-ALA fluorescence were representative according to our neuroimaging and histopathological criteria (positive predictive value of 100%). Our data indicate that strong 5-ALA fluorescence is a reliable and immediately available intraoperative marker of representative tumor tissue of malignant gliomas and intracranial lymphomas in stereotactic biopsies. Thereby, the application of 5-ALA in stereotactic brain tumor biopsies may in future reduce costs for operating room and neuropathology and may decrease procedure-related morbidity.

Quantitative assessment of cardiac output and left ventricular function by noninvasive phase-contrast and cine MRI: validation study with invasive pressure-volume loop analysis in a swine model.

PURPOSE: To validate noninvasive cardiac output measurements of phase-contrast magnetic resonance imaging (PC-MRI) and cine MRI using an invasive pressure-volume (PV) loop technique on a swine model. MATERIALS AND METHODS: We compared three methods for evaluating cardiac function at rest and under pharmaceutical low-dose inotropic infusion conditions: 1) phase-contrast MRI, 2) cine MRI, and 3) PV loop relationship. These measurements were made in 14 domestic pigs under rest conditions. Identical MRI acquisitions and PV loop analysis were performed on six pigs from the same group that received an infusion of dobutamine 2.5 µg/kg/min. Cardiac outputs from all measurements were analyzed and compared using linear regression and Bland-Altman analysis. RESULTS: Noninvasive PC-MRI and cine MRI did not show any significant differences compared to an invasive PV loop technique for measurement of cardiac output under both rest (PC-MRI, cine MRI, and PV loop, 3.17 ± 0.45, 3.18 ± 0.61, 3.45 ± 0.41 L/min, respectively) and pharmaceutical low-dose inotropic infusion conditions (PC-MRI, cine MRI, and PV loop, 4.78 ± 0.53, 4.7 ± 0.6, 4.96 ± 0.48 L/min, respectively). Statistical analysis showed good agreement of cardiac output measurements at rest (R(2) = 0.83) and under low-dose inotropic infusion conditions (R(2) = 0.74) using PC-MRI and PV loop techniques. Cardiac output measurement using cine MRI and PV loop techniques also showed good agreement at rest (R(2) = 0.85) and under low-dose inotropic infusion conditions (R(2) = 0.76). Furthermore, cardiac outputs determined with the three modalities showed good agreement over a wide range of heart rates (90-180 bpm). CONCLUSION: MRI can provide a reliable, noninvasive measurement of cardiac output that can be carried out without the complications that are inherent with current invasive procedures.