Controlled mechanical ventilation to detect regional lymph node metastases in esophageal cancer using USPIO-enhanced MRI; comparison of image quality.

BACKGROUND: Artifacts caused by respiratory motion or ventilation-induced chest movements are a major problem for thoracic MRI, as they can obscure important anatomical structures such as lymph node metastases. We compared image quality of routine breathhold with intermittent apnea during controlled mechanical ventilation of patients under general anesthesia as the ideal situation without respiratory motion in the detection and characterization of regional lymph nodes in esophageal cancer. METHODS: In this prospective study, 10 patients treated for esophageal cancer underwent ultrasmall superparamagnetic iron oxide (USPIO) enhanced MRI scans. Before neoadjuvant therapy, MRI scans were acquired with a routine breathhold technique. After neoadjuvant therapy, patients were scanned under general anesthesia immediately prior to surgery with controlled mechanical ventilation. The image quality was compared using a Likert scale questionnaire based on visibility of anatomical structures and image artifacts. RESULTS: MRI with controlled mechanical ventilation and prolonged controlled apnea of 4 min was safe and feasible. All cardio-respiratory monitoring parameters remained stable during the apnea phases. Mediastinal and upper abdominal lymph nodes down to 2 mm in size could be visualized with all sequences. All image quality criteria, including visibility of thoracic structures and regional lymph nodes were scored higher using the controlled ventilation sequences compared to the routine breathhold phase. CONCLUSION: USPIO-enhanced MRI with controlled mechanical ventilation is superior to routine breathhold MRI in visualizing lymph nodes, which warrants new motion reduction techniques to use MRI for the detection of lymph node metastases in patients with esophageal cancer.

68Ga-PSMA-PET/CT and Diffusion MRI Targeting for Cone-Beam CT-Guided Bone Biopsies of Castration-Resistant Prostate Cancer Patients.

INTRODUCTION: Precision medicine expands the treatment options for metastatic castration-resistant prostate cancer (mCRPC) by targeting druggable genetic aberrations. Aberrations can be identified following molecular analysis of metastatic tissue. Bone metastases, commonly present in mCRPC, hinder precision medicine due to a high proportion of biopsies with insufficient tumor cells for next-generation DNA sequencing. We aimed to investigate the feasibility of incorporating advanced target planning and needle guidance in bone biopsies and whether this procedure increases biopsy tumor yield and success rate of molecular analysis as compared to the current standards, utilizing only CT guidance. MATERIALS AND METHODS: In a pilot study, ten mCRPC patients received 68Ga-prostate-specific membrane antigen (PSMA)-PET/CT and diffusion-weighted MRI as biopsy planning images. These datasets were fused for targeting metastatic lesions with high tumor densities. Biopsies were performed under cone-beam CT (CBCT) guidance. Feasibility of target planning and needle guidance was assessed, and success of molecular analysis and tumor yield were reported. RESULTS: Fusion target planning and CBCT needle guidance were feasible. Nine out of ten biopsies contained prostate cancer cells, with a median of 39% and 40% tumor cells by two different sequencing techniques. Molecular analysis was successful in eight of ten patients (80%). This exceeds previous reports on CT-guided biopsies that ranged from 33 to 44%. In two patients, important druggable aberrations were found. DISCUSSION: A biopsy procedure using advanced target planning and needle guidance is feasible and can increase the success rate of molecular analysis in bone metastases, thereby having the potential of improving treatment outcome for patients with mCRPC. LEVEL OF EVIDENCE: Level 4, case series.

Multi-center reproducibility of neurochemical profiles in the human brain at 7 T.

The purpose of this work was to harmonize data acquisition and post-processing of single voxel proton MRS ((1) H-MRS) at 7 T, and to determine metabolite concentrations and the accuracy and reproducibility of metabolite levels in the adult human brain. This study was performed in compliance with local institutional human ethics committees. The same seven subjects were each examined twice using four different 7 T MR systems from two different vendors using an identical semi-localization by adiabatic selective refocusing spectroscopy sequence. Neurochemical profiles were obtained from the posterior cingulate cortex (gray matter, GM) and the corona radiata (white matter, WM). Spectra were analyzed with LCModel, and sources of variation in concentrations ('subject', 'institute' and 'random') were identified with a variance component analysis. Concentrations of 10-11 metabolites, which were corrected for T1 , T2 , magnetization transfer effects and partial volume effects, were obtained with mean Cramér-Rao lower bounds below 20%. Data variances and mean concentrations in GM and WM were comparable for all institutions. The primary source of variance for glutamate, myo-inositol, scyllo-inositol, total creatine and total choline was between subjects. Variance sources for all other metabolites were associated with within-subject and system noise, except for total N-acetylaspartate, glutamine and glutathione, which were related to differences in signal-to-noise ratio and in shimming performance between vendors. After multi-center harmonization of acquisition and post-processing protocols, metabolite concentrations and the sizes and sources of their variations were established for neurochemical profiles in the healthy brain at 7 T, which can be used as guidance in future studies quantifying metabolite and neurotransmitter concentrations with (1) H-MRS at ultra-high magnetic field.

Image quality and cancer visibility of T2-weighted magnetic resonance imaging of the prostate at 7 Tesla.

OBJECTIVES: To assess the image quality of T2-weighted (T2w) magnetic resonance imaging of the prostate and the visibility of prostate cancer at 7 Tesla (T). MATERIALS & METHODS: Seventeen prostate cancer patients underwent T2w imaging at 7T with only an external transmit/receive array coil. Three radiologists independently scored images for image quality, visibility of anatomical structures, and presence of artefacts. Krippendorff's alpha and weighted kappa statistics were used to assess inter-observer agreement. Visibility of prostate cancer lesions was assessed by directly linking the T2w images to the confirmed location of prostate cancer on histopathology. RESULTS: T2w imaging at 7T was achievable with 'satisfactory' (3/5) to 'good' (4/5) quality. Visibility of anatomical structures was predominantly scored as 'satisfactory' (3/5) and 'good' (4/5). If artefacts were present, they were mostly motion artefacts and, to a lesser extent, aliasing artefacts and noise. Krippendorff's analysis revealed an α = 0.44 between three readers for the overall image quality scores. Clinically significant cancer lesions in both peripheral zone and transition zone were visible at 7T. CONCLUSION: T2w imaging with satisfactory to good quality can be routinely acquired, and cancer lesions were visible in patients with prostate cancer at 7T using only an external transmit/receive body array coil. KEY POINTS: • Satisfactory to good T2-weighted image quality of the prostate is achievable at 7T. • Periprostatic lipids appear hypo-intense compared to healthy peripheral zone tissue at 7T. • Prostate cancer is visible on T2-weighted MRI at 7T.

The diagnostic accuracy and cost-effectiveness of magnetic resonance spectroscopy and enhanced magnetic resonance imaging techniques in aiding the localisation of prostate abnormalities for biopsy: a systematic review and economic evaluation.

BACKGROUND: In the UK, prostate cancer (PC) is the most common cancer in men. A diagnosis can be confirmed only following a prostate biopsy. Many men find themselves with an elevated prostate-specific antigen (PSA) level and a negative biopsy. The best way to manage these men remains uncertain. OBJECTIVES: To assess the diagnostic accuracy of magnetic resonance spectroscopy (MRS) and enhanced magnetic resonance imaging (MRI) techniques [dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted MRI (DW-MRI)] and the clinical effectiveness and cost-effectiveness of strategies involving their use in aiding the localisation of prostate abnormalities for biopsy in patients with prior negative biopsy who remain clinically suspicious for harbouring malignancy. DATA SOURCES: Databases searched--MEDLINE (1946 to March 2012), MEDLINE In-Process & Other Non-Indexed Citations (March 2012), EMBASE (1980 to March 2012), Bioscience Information Service (BIOSIS; 1995 to March 2012), Science Citation Index (SCI; 1995 to March 2012), The Cochrane Library (Issue 3 2012), Database of Abstracts of Reviews of Effects (DARE; March 2012), Medion (March 2012) and Health Technology Assessment database (March 2012). REVIEW METHODS: Types of studies: direct studies/randomised controlled trials reporting diagnostic outcomes. INDEX TESTS: MRS, DCE-MRI and DW-MRI. Comparators: T2-weighted magnetic resonance imaging (T2-MRI), transrectal ultrasound-guided biopsy (TRUS/Bx). Reference standard: histopathological assessment of biopsied tissue. A Markov model was developed to assess the cost-effectiveness of alternative MRS/MRI sequences to direct TRUS-guided biopsies compared with systematic extended-cores TRUS-guided biopsies. A health service provider perspective was adopted and the recommended 3.5% discount rate was applied to costs and outcomes. RESULTS: A total of 51 studies were included. In pooled estimates, sensitivity [95% confidence interval (CI)] was highest for MRS (92%; 95% CI 86% to 95%). Specificity was highest for TRUS (imaging test) (81%; 95% CI 77% to 85%). Lifetime costs ranged from £3895 using systematic TRUS-guided biopsies to £4056 using findings on T2-MRI or DCE-MRI to direct biopsies (60-year-old cohort, cancer prevalence 24%). The base-case incremental cost-effectiveness ratio for T2-MRI was <£30,000 per QALY (all cohorts). Probabilistic sensitivity analysis showed high uncertainty surrounding the incremental cost-effectiveness of T2-MRI in moderate prevalence cohorts. The cost-effectiveness of MRS compared with T2-MRI and TRUS was sensitive to several key parameters. LIMITATIONS: Non-English-language studies were excluded. Few studies reported DCE-MRI/DW-MRI. The modelling was hampered by limited data on the relative diagnostic accuracy of alternative strategies, the natural history of cancer detected at repeat biopsy, and the impact of diagnosis and treatment on disease progression and health-related quality of life. CONCLUSIONS: MRS had higher sensitivity and specificity than T2-MRI. Relative cost-effectiveness of alternative strategies was sensitive to key parameters/assumptions. Under certain circumstances T2-MRI may be cost-effective compared with systematic TRUS. If MRS and DW-MRI can be shown to have high sensitivity for detecting moderate/high-risk cancer, while negating patients with no cancer/low-risk disease to undergo biopsy, their use could represent a cost-effective approach to diagnosis. However, owing to the relative paucity of reliable data, further studies are required. In particular, prospective studies are required in men with suspected PC and elevated PSA levels but previously negative biopsy comparing the utility of the individual and combined components of a multiparametric magnetic resonance (MR) approach (MRS, DCE-MRI and DW-MRI) with both a MR-guided/-directed biopsy session and an extended 14-core TRUS-guided biopsy scheme against a reference standard of histopathological assessment of biopsied tissue obtained via saturation biopsy, template biopsy or prostatectomy specimens. STUDY REGISTRATION: PROSPERO number CRD42011001376. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Quantitative short echo time 1H MRSI of the peripheral edematous region of human brain tumors in the differentiation between glioblastoma, metastasis, and meningioma.

PURPOSE: To assess metabolite levels in peritumoral edematous (PO) and surrounding apparently normal (SAN) brain regions of glioblastoma, metastasis, and meningioma in humans with (1)H-MRSI to find biomarkers that can discriminate between tumors and characterize infiltrative tumor growth. MATERIALS AND METHODS: Magnetic resonance (MR) spectra (semi-LASER MRSI, 30 msec echo time, 3T) were selected from regions of interest (ROIs) under MRI guidance, and after quality control of MR spectra. Statistical testing between patient groups was performed for mean metabolite ratios of an entire ROI and for the highest value within that ROI. RESULTS: The highest ratios of the level of choline compounds and the sum of myo-inositol and glycine over N-acetylaspartate and creatine compounds were significantly increased in PO regions of glioblastoma versus that of metastasis and meningioma. In the SAN region of glioblastoma some of these ratios were increased. Differences were less prominent for metabolite levels averaged over entire ROIs. CONCLUSION: Specific metabolite ratios in PO and SAN regions can be used to discriminate glioblastoma from metastasis and meningioma. An analysis of these ratios averaged over entire ROIs and those with most abnormal values indicates that infiltrative tumor growth in glioblastoma is inhomogeneous and extends into the SAN region.

Imaging vascular function for early stage clinical trials using dynamic contrast-enhanced magnetic resonance imaging.

Many therapeutic approaches to cancer affect the tumour vasculature, either indirectly or as a direct target. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has become an important means of investigating this action, both pre-clinically and in early stage clinical trials. For such trials, it is essential that the measurement process (i.e. image acquisition and analysis) can be performed effectively and with consistency among contributing centres. As the technique continues to develop in order to provide potential improvements in sensitivity and physiological relevance, there is considerable scope for between-centre variation in techniques. A workshop was convened by the Imaging Committee of the Experimental Cancer Medicine Centres (ECMC) to review the current status of DCE-MRI and to provide recommendations on how the technique can best be used for early stage trials. This review and the consequent recommendations are summarised here. Key Points • Tumour vascular function is key to tumour development and treatment • Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess tumour vascular function • Thus DCE-MRI with pharmacokinetic models can assess novel treatments • Many recent developments are advancing the accuracy of and information from DCE-MRI • Establishing common methodology across multiple centres is challenging and requires accepted guidelines.

Detection of fully refocused polyamine spins in prostate cancer at 7 T.

(1)H MRSI is often used at 1.5 or 3 T to study prostate cancer, where the ratio of choline + creatine to citrate is taken as a marker for tumour presence. Recently, the level of polyamines (mainly spermine) has been shown to improve specificity even further. However, the in vivo detection of these polyamines (at 3.1 ppm) is hampered by signal cancellation as a result of J-coupling effects and signal overlap with choline (3.2 ppm) and creatine (3.0 ppm) resonances. At higher magnetic field strengths, the chemical shift dispersion will increase, which allows the use of very selective radiofrequency pulses to refocus J-coupled spins. In this work, we added selective refocusing pulses to a semi-LASER (localisation based on adiabatic selective refocusing) sequence at 7 T, and optimised the inter-pulse timings of the sequence for fully refocused detection of spermine spins, whilst maintaining optimised detection of choline, creatine and the strongly coupled spin system of citrate.

31P magnetic resonance spectroscopic imaging with polarisation transfer of phosphomono- and diesters at 3 T in the human brain: relation with age and spatial differences.

Tissue levels of the compounds phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE) can be studied by in vivo 31P MRS. However, the detection of the signals of these compounds suffers from low sensitivity and contamination by underlying broad resonances of other phosphorylated compounds. Improved sensitivity without this contamination can be achieved with a method for optimal polarisation transfer of 1H to 31P spins in these molecules, called selective refocused insensitive nuclei-enhanced polarisation transfer (sRINEPT). The aim of this study was to implement a three-dimensional magnetic resonance spectroscopic imaging (MRSI) version of sRINEPT on a clinical 3 T magnetic resonance system to obtain spatially resolved relative levels of PC, PE, GPC and GPE in the human brain as a function of age, which could be used as a reference dataset for clinical applications. Good signal-to-noise ratios were obtained from voxels of 17 cm(3) of the parietal and occipital lobes of the brain within a clinically acceptable measurement time of 17 min. Eighteen healthy subjects of different ages (16-70 years) were examined with this method. A strong inverse relation of the PE/GPE and PC/GPC ratios with age was found. Spatial resolution was sufficient to detect differences in metabolite ratios between white and grey matter. Moreover, we showed the feasibility of this method for clinical use in a pilot study of patients with brain tumours. The sRINEPT MRSI technique enables the exploration of phospholipid metabolism in brain diseases with a better sensitivity than was possible with earlier 31P MRS methods.

Proton spectroscopic imaging of the human prostate at 7 T.

The sensitivity of proton MR Spectroscopic Imaging ((1)H-MRSI) of the prostate can be optimized by using the high magnetic field strength of 7 T in combination with an endorectal coil. In the work described in this paper we introduce an endorectal transceiver at 7 T, validate its safety for in vivo use and apply a pulse sequence, optimized for three-dimensional (3D) (1)H-MRSI of the human prostate at 7 T. A transmit/receive endorectal RF coil was adapted from a commercially available 3 T endorectal receive-only coil and validated to remain within safety guidelines for radiofrequency (RF) power deposition using numerical models, MR thermometry of phantoms, and in vivo temperature measurements. The (1)H-MRSI pulse sequence used adiabatic slice selective refocusing pulses and frequency-selective water and lipid suppression to selectively obtain the relevant metabolite signals from the prostate. Quantum mechanical simulations were used to adjust the inter-pulse timing for optimal detection of the strongly coupled spin system of citrate resulting in an echo time of 56 ms. Using this endorectal transceiver and pulse sequence with slice selective adiabatic refocusing pulses, 3D (1)H-MRSI of the human prostate is feasible at 7 T with a repetition time of 2 s. The optimized inter-pulse timing enables the absorptive detection of resonances of spins from spermine and citrate in phase with creatine and choline. These potential tumor markers may improve the in vivo detection, localization, and assessment of prostate cancer.

Efficient 1H to 31P polarization transfer on a clinical 3T MR system.

31P MR spectroscopy (MRS) in the detection of phosphocholine (PC), glycerolphosphocholine (GPC), phosphorylelthanolamine (PE), and glycerolphosphoethanolamine (GPE) compounds has shown clinical potential at 1.5T for several human diseases. The use of (1)H to (31)P polarization transfer can improve the sensitivity using a refocused INEPT method with a potential enhancement of 2.4 (gamma(1H)/gamma(31P)). However, in this method the (31)P signals of PE, PC, GPE, and GPC are strongly attenuated (50% or more) due to J-coupling between (31)P and (1)H that have similar magnitudes for homonuclear J-coupling constants in those metabolites. A method to cancel the homonuclear J-coupling effects in polarization transfer experiments is to apply frequency-selective refocusing pulses, which becomes feasible at 3T due to the increased chemical shift dispersion as compared to 1.5T. In this study, full (1)H to (31)P polarization transfer was realized using chemical shift selective refocusing pulses at 3T. T(1) and T(2) values for (1)H and (31)P spins of PE, PC, GPE, and GPC were measured in the human brain. A more than 2-fold signal-to-noise ratio (SNR) improvement was obtained compared to an optimized direct (31)P MRS method. As shifted RF pulses were used, this method can be applied on a broadband clinical MR system with a single RF system.

Intact plant magnetic resonance imaging to study dynamics in long-distance sap flow and flow-conducting surface area.

Due to the fragile pressure gradients present in the xylem and phloem, methods to study sap flow must be minimally invasive. Magnetic resonance imaging (MRI) meets this condition. A dedicated MRI method to study sap flow has been applied to quantify long-distance xylem flow and hydraulics in an intact cucumber (Cucumis sativus) plant. The accuracy of this MRI method to quantify sap flow and effective flow-conducting area is demonstrated by measuring the flow characteristics of the water in a virtual slice through the stem and comparing the results with water uptake data and microscopy. The in-plane image resolution of 120 x 120 microm was high enough to distinguish large individual xylem vessels. Cooling the roots of the plant severely inhibited water uptake by the roots and increased the hydraulic resistance of the plant stem. This increase is at least partially due to the formation of embolisms in the xylem vessels. Refilling the larger vessels seems to be a lengthy process. Refilling started in the night after root cooling and continued while neighboring vessels at a distance of not more than 0.4 mm transported an equal amount of water as before root cooling. Relative differences in volume flow in different vascular bundles suggest differences in xylem tension for different vascular bundles. The amount of data and detail that are presented for this single plant demonstrates new possibilities for using MRI in studying the dynamics of long-distance transport in plants.

Microscopic imaging of slow flow and diffusion: a pulsed field gradient stimulated echo sequence combined with turbo spin echo imaging.

In this paper we present a pulse sequence that combines a displacement-encoded stimulated echo with rapid sampling of k-space by means of turbo spin echo imaging. The stimulated echo enables the use of long observation times between the two pulsed field gradients that sample q-space completely. Propagators, constructed with long observation times, could discriminate slowly flowing protons from diffusing protons, as shown in a phantom in which a plug flow with linear velocity of 50microm/s could clearly be distinguished from stationary water. As a biological application the apparent diffusion constant in longitudinal direction of a transverse image of a maize plant stem had been measured as a function of observation time. Increasing contrast in the apparent diffusion constant image with increasing observation times were caused by differences in plant tissue: although the plant stem did not take up any water, the vascular bundles, concentrated in the outer ring of the stem, could still be discerned because of their longer unrestricted diffusional pathways for water in the longitudinal direction compared to cells in the parenchymal tissue. In the xylem region of a tomato pedicel flowing water could be distinguished from a large amount of stationary water. Linear flow velocities up to 0.67 mm/s were measured with an observation time of 180 ms.

Using NMR displacement imaging to characterize electroosmotic flow in porous media.

Pulsed field gradient nuclear magnetic resonance (PFG-NMR) and NMR imaging were used to study temporal and spatial domains of an electrokinetically-driven mobile phase through open and packed segments of capillaries. Characteristics like velocity distribution and an asymptotic dispersion are contrasted to viscous flow behavior. We show that electroosmotic flow in microchannel geometries can offer a significant performance advantage over the pressure-driven flows at comparable Peclét numbers, indicating that velocity extremes in the pore space of open tubes and packed beds are drastically reduced. An inherent problem of capillary electrochromatography that we finally address is the existence of wall effects when in the general case the surface zeta-potentials of the capillary inner wall and the adsorbent particles are different. Using dynamic NMR microscopy we were able resolve this systematic velocity inequality of the flow pattern which strongly influences axial dispersion and may be responsible for long time-tails of velocity distribution in the mobile phase.

Quantification of water transport in plants with NMR imaging.

A new nuclear magnetic resonance imaging (NMRi) method is described to calculate the characteristics of water transport in plant stems. Here, dynamic NMRi is used as a non-invasive technique to record the distribution of displacements of protons for each pixel in the NMR image. Using the NMR-signal of the stationary water in a reference tube for calibration, the following characteristics can be calculated per pixel without advance knowledge of the flow-profile in that pixel: the amount of stationary water, the amount of flowing water, the cross-sectional area of flow, the average linear flow velocity of the flowing water, and the volume flow. The accuracy of the method is demonstrated with a stem segment of a chrysanthemum flower by comparing the volume flow, measured with NMR, with the actual volumetric uptake, measured with a balance. NMR measurements corresponded to the balance uptake measurements with a rms error of 0.11 mg s(-1) in a range of 0 to 1.8 mg s(-1). Local changes in flow characteristics of individual voxels of a sample (e.g. intact plant) can be studied as a function of time and of any conceivable changes the sample experiences on a time-scale, longer than the measurement time of a complete set of pixel-propagators (17 min).

Microscopic displacement imaging with pulsed field gradient turbo spin-echo NMR.

We present a pulse sequence that enables the accurate and spatially resolved measurements of the displacements of spins in a variety of (biological) systems. The pulse sequence combines pulsed field gradient (PFG) NMR with turbo spin-echo (TSE) imaging. It is shown here that by ensuring that the phase of the echoes within a normal spin-echo train is constant, displacement propagators can be generated on a pixel-by-pixel basis. These propagators accurately describe the distribution of displacements, while imaging time is decreased by using separate phase encoding for every echo in a TSE train. Measurements at 0.47 T on two phantoms and the stem of an intact tomato plant demonstrate the capability of the sequence to measure complete and accurate propagators, encoded with 16 PFG steps, for each pixel in a 128 x 128 image (resolution 117 x 117 x 3,000 microm) within 17 min. Dynamic displacement studies on a physiologically relevant time resolution for plants are now within reach.