Evaluation of response in patients with hepatocellular carcinoma treated with intratumoral dendritic cell vaccination using intravoxel incoherent motion (IVIM) MRI and histogram analysis.

BACKGROUND: Immunotherapy of hepatocellular carcinoma (HCC) is an emerging method with promising results. Immunotherapy can have an antitumor effect without affecting tumor size, calling for functional imaging methods for response evaluation. PURPOSE: To evaluate the response to intratumoral injections with the immune primer ilixadencel in HCCs with diffusion-weighted magnetic resonance imaging (DW-MRI) using intravoxel incoherent motion (IVIM) and histogram analysis. MATERIAL AND METHODS: A total of 17 patients with advanced HCC were treated with intratumoral injections with ilixadencel on three occasions 2-5 weeks apart. The patients were examined with IVIM before each injection as well as approximately three months after the first injection. RESULTS: The 10th percentile of perfusion-related parameter D* decreased significantly after the first and second intratumoral injections of ilixadencel compared to baseline (P < 0.05). There was a non-significant trend of lower median region of interest f (perfusion fraction) before injection 2 compared to baseline (P = 0.07). There were significant correlations between the 10th percentile and median of D at baseline and change in tumor size after three months (r = 0.79, P < 0.01 and r = 0.72, P < 0.05, respectively). CONCLUSION: DW-MRI with IVIM and histogram analysis revealed significant reductions of D* early after treatment as well as an association between D at baseline and smaller tumor growth at three months. The lower percentiles (10th and 50th) were found more important. Further research is needed to confirm our preliminary findings of reduced perfusion after ilixadencel vaccinations, suggesting a treatment effect on HCC.

VERDICT MRI for radiation treatment response assessment in neuroendocrine tumors.

Noninvasive methods to study changes in tumor microstructure enable early assessment of treatment response and thus facilitate personalized treatment. The aim of this study was to evaluate the diffusion MRI model, Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumors (VERDICT), for early response assessment to external radiation treatment and to compare the results with those of more studied sets of parameters derived from diffusion-weighted MRI data. Mice xenografted with human small intestine tumors were treated with external radiation treatment, and diffusion MRI experiments were performed on the day before and up to 2 weeks after treatment. The diffusion models VERDICT, ADC, IVIM, and DKI were fitted to MRI data, and the treatment response of each tumor was calculated based on pretreatment tumor growth and post-treatment tumor volume regression. Linear regression and correlation analysis were used to evaluate each model and their respective parameters for explaining the treatment response. VERDICT analysis showed significant changes from day -1 to day 3 for the intracellular and extracellular volume fraction, as well as the cell radius index (p < 0.05; Wilcoxon signed-rank test). The strongest correlation between the diffusion model parameters and the tumor treatment response was seen for the ADC, kurtosis-corrected diffusion coefficient, and intracellular volume fraction on day 3 (τ = 0.47, 0.52, and -0.49, respectively, p < 0.05; Kendall rank correlation coefficient). Of all the tested models, VERDICT held the strongest explanatory value for the tumor treatment response on day 3 (R2  = 0.75, p < 0.01; linear regression). In conclusion, VERDICT has potential for early assessment of external radiation treatment and may provide further insights into the underlying biological effects of radiation on tumor tissue. In addition, the results suggest that the time window for assessment of treatment response using dMRI may be narrow.

Head and neck cancer patient positioning using synthetic CT data in MRI-only radiation therapy.

PURPOSE: The accuracy and precision of patient positioning is crucial in radiotherapy; however, there are no publications available using synthetic computed tomography (sCT) that evaluate rotations in head and neck (H&N) patients positioning or the effect of translation and rotation combined. The aim of this work was to evaluate the differences between using sCT with the CT for 2D- and 3D-patient positioning in a magnetic resonance imaging (MRI)-only workflow. METHODS: This study included 14 H&N cancer patients, with generated sCT data (MRI Planner v2.2) and the CT deformably registered to the MRI. Patient positioning was evaluated by comparing sCT against CT data: 3D cone beam CT (CBCT) was registered to the deformed CT (dCT) and sCT in six degrees of freedom (DoF) with a rigid auto-registration algorithm and bone threshold, and 2D deformed digital reconstructed radiographs (dDRR) and synthetic DRRs (sDRR) were manually registered to orthogonal projections in five DoF by six blinded observers. The difference in displacement in all DoF were calculated for dCT and sCT, as well as for dDRR and sDRR. The interobserver variation was evaluated by separate application of the paired dDRR and sDRR registration matrices to the original coordinates of the planning target volume (PTV) structures and calculation of the Euclidean distance between the corresponding points. The Dice similarity coefficient (DSC) was calculated between dDRR/sDRR-registered PTVs. RESULTS: The mean difference in patient positioning using CBCT was <0.7 mm and <0.3° and using orthogonal projections <0.4 mm and <0.2° in all directions. The maximum Euclidean distance was 5.1 mm, the corresponding mean (1SD) Euclidean distance and mean DSC were 3.5 ± 0.7 mm and 0.93, respectively. CONCLUSIONS: This study shows that the sCT-based patient positioning gives a comparable result with that based on CT images, allowing sCT to replace CT as reference for patient treatment positioning.

Neurochemical properties measured by 1H magnetic resonance spectroscopy may predict cognitive behaviour therapy outcome in paediatric OCD: a pilot study.

To identify neurochemical factors measured pre-treatment that may predict cognitive behavioural treatment (CBT) outcome, aiming at understanding possible causes of poor CBT response. 1H magnetic resonance spectroscopy was used before treatment with CBT in treatment naïve 11-18 year-old patients with moderate-severe OCD. Diagnoses and assessment of OCD severity were based on semi-structured interviews. Linear mixed effects models were used to analyse the association between metabolite level and treatment outcome. Worse CBT outcome was associated with higher concentration of glutamine and glutamate combined (Glx) in middle cingulate cortex (MCC) (F = + 3.35, p = 0.004) and of N-acetylaspartate and N-acetylaspartylglutamate combined (tNAA) (F = + 2.59, p = 0.019). Also, we noted a tendency towards higher thalamic Glx concentration (F = + 1.91, p = 0.077) to be associated with worse CBT outcome. In general, the findings of the current pilot study are compatible with the hypothesis of an overweight of excitatory to inhibitory factors in brain circuits driving goal-directed behaviours (GDB). Higher MCC Glx and tNAA may be involved in the selection of GDB. A more detailed understanding of how these brain areas function in health and illness is needed.

Simulated basis sets for semi-LASER: the impact of including shaped RF pulses and magnetic field gradients.

OBJECTIVE: To study the need for inclusion of shaped RF pulses and magnetic field gradients in simulations of basis sets for the analysis of proton MR spectra of single voxels of the brain acquired with a semi-LASER pulse sequence. MATERIALS AND METHODS: MRS basis sets where simulated at different echo times with hard RF pulses as well as with shaped RF pulses without or with magnetic field gradients included. The influence on metabolite concentration quantification was assessed using both phantom and in vivo measurements. For comparison, simulations and measurements were performed with the PRESS pulse sequence. RESULTS: The effect of including gradients in the simulations was smaller for semi-LASER than for PRESS, however, still noticeable. The difference was larger for strongly coupled metabolites and at longer echo times. Metabolite quantification using semi-LASER was thereby less dependent on the inclusion of gradients than PRESS, which was seen in both phantom and in vivo measurements. DISCUSSION: The inclusion of the shaped RF pulses and magnetic field gradients in the simulation of basis sets for semi-LASER is only important for strongly coupled metabolites. If computational time is a limiting factor, simple simulations with hard RF pulses can provide almost as accurate metabolite quantification as those that include the chemical-shift related displacement.

Optimization of b-value schemes for estimation of the diffusion coefficient and the perfusion fraction with segmented intravoxel incoherent motion model fitting.

PURPOSE: Intravoxel incoherent motion (IVIM) modeling for estimation of the diffusion coefficient (D) and perfusion fraction (f) is increasingly popular, but no consensus on standard protocols exists. This study provides a framework for optimization of b-value schemes for reduced estimation uncertainty of D and f from segmented model fitting. THEORY: Analytical expressions for uncertainties of D and f from segmented model fitting were derived as Cramer-Rao lower bounds (CRLBs). METHODS: Optimized b-value schemes were obtained for 3 to 12 acquisitions and in the limit of infinitely many acquisitions through constrained minimization of the CRLBs, with b-values constrained to be 0 or 200 to 800 s/mm2 . The optimized b-value scheme with eight acquisitions was compared with b-values linearly distributed in the allowed range using simulations and in vivo liver data from seven healthy volunteers. RESULTS: All optimized b-value schemes contained exactly three unique b-values regardless of the total number of acquisitions (0, 200, and 800 s/mm2 ) with repeated acquisitions distributed approximately as 1:2:2. Compared with linearly distributed b-values, the variability of estimates of D and f was reduced by approximately 30% as seen both in simulations and in repeated in vivo measurements. CONCLUSION: The uncertainty of IVIM D and f estimates can be reduced by the use of optimized b-value schemes.

Data-driven identification of tumor subregions based on intravoxel incoherent motion reveals association with proliferative activity.

PURPOSE: Intravoxel incoherent motion (IVIM) analysis gives information on tissue diffusion and perfusion and may thus have a potential for e.g. tumor tissue characterization. This work aims to study if clustering based on IVIM parameter maps can identify tumor subregions, and to assess the relevance of obtained subregions by histological analysis. METHODS: Fourteen mice with human neuroendocrine tumors were examined with diffusion-weighted imaging to obtain IVIM parameter maps. Gaussian mixture models with IVIM maps from all tumors as input were used to partition voxels into k clusters, where k = 2 was chosen for further analysis based on goodness of fit. Clustering was performed with and without the perfusion-related IVIM parameter D* , and with and without including spatial information. The validity of the clustering was assessed by comparison with corresponding histologically stained tumor sections. A Ki-67-based index quantifying the degree of tumor proliferation was considered appropriate for the comparison based on the obtained cluster characteristics. RESULTS: The clustering resulted in one class with low diffusion and high perfusion and another with slightly higher diffusion and low perfusion. Strong agreement was found between tumor subregions identified by clustering and subregions identified by histological analysis, both regarding size and spatial agreement. Neither D* nor spatial information had substantial effects on the clustering results. CONCLUSIONS: The results of this study show that IVIM parameter maps can be used to identify tumor subregions using a data-driven framework based on Gaussian mixture models. In the studied tumor model, the obtained subregions showed agreement with proliferative activity.

Multiparametric MR for non-invasive evaluation of tumour tissue histological characteristics after radionuclide therapy.

Early non-invasive tumour therapy response assessment requires methods sensitive to biological and physiological tumour characteristics. The aim of this study was to find and evaluate magnetic resonance imaging (MRI) derived tumour tissue parameters that correlate with histological parameters and that reflect effects of radionuclide therapy. Mice bearing a subcutaneous human small-intestine neuroendocrine tumour were i.v. injected with 177 Lu-octreotate. MRI was performed (7 T Bruker Biospec) on different post-therapy intervals (1 and 13 days) using T2-weighted imaging, mapping of T2* and T1 relaxation time constants, as well as diffusion and dynamic contrast enhancement (DCE-MRI) techniques. After MRI, animals were killed and tumours excised. Four differently stained histological sections of the most central imaged tumour plane were digitized, and segmentation techniques were used to produce maps reflecting fibrotic and vascular density, apoptosis, and proliferation. Histological maps were aligned with MRI-derived parametric maps using landmark-based registration. Correlations and predictive power were evaluated using linear mixed-effects models and cross-validation, respectively. Several MR parameters showed statistically significant correlations with histological parameters. In particular, three DCE-MRI-derived parameters reflecting capillary function additionally showed high predictive power regarding apoptosis (2/3) and proliferation (1/3). T1 could be used to predict vascular density, and perfusion fraction derived from diffusion MRI could predict fibrotic density, although with lower predictive power. This work demonstrates the potential to use multiparametric MRI to retrieve important information on the tumour microenvironment after radiotherapy. The non-invasiveness of the method also allows longitudinal tumour tissue characterization. Further investigation is warranted to evaluate the parameters highlighted in this study longitudinally, in larger studies, and with additional histological methods.

Impact of prior distributions and central tendency measures on Bayesian intravoxel incoherent motion model fitting.

PURPOSE: Bayesian model fitting has been proposed as a robust alternative for intravoxel incoherent motion (IVIM) model-fitting parameter estimation. However, consensus regarding choice of prior distribution and posterior distribution central tendency measure is needed. The aim of this study was to compare the quality of IVIM parameter estimates produced by different prior distributions and central tendency measures, and to gain knowledge about the effect of these choices. METHODS: Three prior distributions (uniform, reciprocal, and lognormal) and two measures of central tendency (mean and mode) found in the literature were studied using simulations and in vivo data from a tumor mouse model. RESULTS: Simulations showed that the uniform and lognormal priors were superior to the reciprocal prior, especially for the parameters D and f and clinically relevant SNR levels. The choice of central tendency measure had less effect on the results, but had some effects on estimation bias. Results based on simulations and in vivo data agreed well, indicating high validity of the simulations. CONCLUSIONS: Choice of prior distribution and central tendency measure affects the results of Bayesian IVIM parameter estimates. This must be considered when comparing results from different studies. The best overall quality of IVIM parameter estimates was obtained using the lognormal prior. Magn Reson Med 79:1674-1683, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Radioembolization Versus Bland Embolization for Hepatic Metastases from Small Intestinal Neuroendocrine Tumors: Short-Term Results of a Randomized Clinical Trial.

BACKGROUND: Radioembolization (RE) with intra-arterial administration of 90Y microspheres is a promising technique for the treatment of liver metastases from small intestinal neuroendocrine tumors (SI-NET) not amenable to surgery or local ablation. However, studies comparing RE to other loco-regional therapies are lacking. The aim of this randomized study was to compare the therapeutic response and safety after RE and bland hepatic arterial embolization (HAE), and to investigate early therapy-induced changes with diffusion-weighted MRI (DWI-MRI). METHODS: Eleven patients were included in a prospective randomized controlled pilot study, six assigned to RE and five to HAE. Response according to RECIST 1.1 using MRI or CT at 3 and 6 months post-treatment was recorded as well as changes in DWI-MRI parameters after 1 month. Data on biochemical tumor response, toxicity, and side effects were also collected. RESULTS: Three months after treatment, all patients in the HAE group showed partial response according to RECIST while none in the RE group did (p = 0.0022). After 6 months, the response rates were 4/5 (80%) and 2/6 (33%) in the HAE and RE groups, respectively (NS). DWI-MRI metrics could not predict RECIST response, but lower pretreatment ADC(120-800) and larger ADC(0-800) increase at 1 month were related to larger decrease in tumor diameter when all tumors were counted. CONCLUSION: HAE resulted in significantly higher RECIST response after 3 months, but no difference compared to RE remained after 6 months. These preliminary findings indicate that HAE remains a safe option for the treatment of liver metastases from SI-NET, and further studies are needed to establish the role of RE and the predictive value of MR-DWI.

Comparison of methods for estimation of the intravoxel incoherent motion (IVIM) diffusion coefficient (D) and perfusion fraction (f).

OBJECTIVE: Intravoxel incoherent motion (IVIM) shows great potential in many applications, e.g., tumor tissue characterization. To reduce image-quality demands, various IVIM analysis approaches restricted to the diffusion coefficient (D) and the perfusion fraction (f) are increasingly being employed. In this work, the impact of estimation approach for D and f is studied. MATERIALS AND METHODS: Four approaches for estimating D and f were studied: segmented IVIM fitting, least-squares fitting of a simplified IVIM model (sIVIM), and Bayesian fitting of the sIVIM model using marginal posterior modes or posterior means. The estimation approaches were evaluated in terms of bias and variability as well as ability for differentiation between tumor and healthy liver tissue using simulated and in vivo data. RESULTS: All estimation approaches had similar variability and ability for differentiation and negligible bias, except for the Bayesian posterior mean of f, which was substantially biased. Combined use of D and f improved tumor-to-liver tissue differentiation compared with using D or f separately. DISCUSSION: The similar performance between estimation approaches renders the segmented one preferable due to lower numerical complexity and shorter computational time. Superior tissue differentiation when combining D and f suggests complementary biologically relevant information.

Metabolic effects of Lactobacillus reuteri DSM 17938 in people with type 2 diabetes: A randomized controlled trial.

AIMS: To investigate the metabolic effects of 12-week oral supplementation with Lactobacillus reuteri DSM 17938 in patients with type 2 diabetes on insulin therapy. MATERIALS AND METHODS: In a double-blind trial, we randomized 46 people with type 2 diabetes to placebo or a low (108 CFU/d) or high dose (1010 CFU/d) of L. reuteri DSM 17938 for 12 weeks. The primary endpoint was the effect of supplementation on glycated haemoglobin (HbA1c). Secondary endpoints were insulin sensitivity (assessed by glucose clamp), liver fat content, body composition, body fat distribution, faecal microbiota composition and serum bile acids. RESULTS: Supplementation with L. reuteri DSM 17938 for 12 weeks did not affect HbA1c, liver steatosis, adiposity or microbiota composition. Participants who received the highest dose of L. reuteri exhibited increases in insulin sensitivity index (ISI) and serum levels of the secondary bile acid deoxycholic acid (DCA) compared with baseline, but these differences were not significant in the between-group analyses. Post hoc analysis showed that participants who responded with increased ISI after L. reuteri supplementation had higher microbial diversity at baseline, and increased serum levels of DCA after supplementation. In addition, increases in DCA levels correlated with improvement in insulin sensitivity in the probiotic recipients. CONCLUSIONS: Intake of L. reuteri DSM 17938 for 12 weeks did not affect HbA1c in people with type 2 diabetes on insulin therapy; however, L. reuteri improved insulin sensitivity in a subset of participants and we propose that high diversity of the gut microbiota at baseline may be important.

Longitudinal changes in diffusion tensor imaging parameters of the corpus callosum between 6 and 12 months after diffuse axonal injury.

BACKGROUND: Magnetic resonance diffusion tensor imaging (MR-DTI) is used increasingly to detect diffuse axonal injury (DAI) after traumatic brain injury (TBI). PRIMARY OBJECTIVE: To investigate changes in the diffusion tensor imaging parameters of the corpus callosum 6 and 12 months after TBI, to optimize the timing of follow-up DTI investigations. A secondary goal was to study the relationship between DTI parameters and outcome. RESEARCH DESIGN: Longitudinal prospective study. METHODS AND PROCEDURES: MR-DTI was performed in 15 patients with suspected DAI, 6 and 12 months post-injury. Sixteen controls were also examined. Fractional anisotropy (FA) and diffusivity (trace) in the corpus callosum were analysed. The outcome measures were the extended Glasgow Outcome Scale and the Barrow Neurological Institute Screen for Higher Cerebral Functions, assessed at 6 and 12 months. MAIN OUTCOMES AND RESULTS: FA decreased and trace increased at 6 and 12 months compared to controls. Trace continued to increase even further between 6 and 12 months, while FA remained unchanged. Patients with the worst outcomes had lower FA and higher trace compared to patients with better outcomes. CONCLUSIONS: DTI parameters have not reached a stable level at 6 months after DAI, but continue to change, probably reflecting an incessant microstructural alteration of the white matter.

1H magnetic resonance spectroscopy evidence for occipital involvement in treatment-naive paediatric obsessive-compulsive disorder.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder leading to considerable distress and disability. Therapies are effective in a majority of paediatric patients, however, many only get partial response. It is therefore important to study the underlying pathophysiology of the disorder. METHODS: 1H magnetic resonance spectroscopy (MRS) was used to study the concentration of brain metabolites in four different locations (cingulate gyrus and sulcus, occipital cortex, thalamus and right caudate nucleus). Treatment-naive children and adolescents with OCD (13 subjects) were compared with a group of healthy age- and gender-matched subjects (11 subjects). Multivariate analyses were performed on the concentration values. RESULTS: No separation between controls and patients was found. However, a correlation between metabolite concentrations and symptom severity as measured with the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) was found. Strongest was the correlation with the CY-BOCS obsession subscore and aspartate and choline in the caudate nucleus (positively correlated with obsessions), lipids at 2 and 0.9 ppm in thalamus, and occipital glutamate+glutamine, N-acetylaspartate and myo-inosytol (negatively correlated with obsessions). CONCLUSIONS: The observed correlations between 1H MRS and CY-BOCS in treatment-naive patients further supports an occipital involvement in OCD. The results are consistent with our previous study on adult OCD patients. The 1H MRS data were not supportive of a separation between the patient and control groups.

Impact of region-of-interest method on quantitative analysis of DTI data in the optic tracts.

BACKGROUND: To extract DTI parameters from a specific structure, a region of interest (ROI) must be defined. ROI selection in small structures is challenging; the final measurement results could be affected due to the significant impact of small geometrical errors. In this study the optic tracts were analyzed with the aim to assess differences in DTI parameters due to ROI method and to identify the most reliable method. METHODS: Images of 20 healthy subjects were acquired. Fractional anisotropy (FA) was extracted from the optic tracts by four different ROI methods. Manual tracing was performed in 1) the b0 image and 2) a T1-weighted image registered to the FA image. Semi-automatic segmentation was performed based on 3) tractography and 4) the FA-skeleton algorithm in the tract-based spatial statistics (TBSS) framework. Results were analyzed with regard to ROI method as well as to inter-scan, intra-rater and inter-rater reliability. RESULTS: The resulting FA values divided the ROI methods into two groups that differed significantly: 1) the FA-skeleton and the b0 methods showed higher FA values compared to 2) the tractography and the T1-weighted methods. The intra- and inter-rater variabilities were similar for all methods, except for the tractography method where the inter-rater variability was higher. The FA-skeleton method had a better reproducibility than the other methods. CONCLUSION: Choice of ROI method was found to be highly influential on FA values when the optic tracts were analyzed. The FA-skeleton method performed the best, yielding low variability and high repeatability.

Tractography of Meyer's loop for temporal lobe resection­validation by prediction of postoperative visual field outcome‬‬‬‬.

BACKGROUND: Postoperative visual field defects are common after temporal lobe resection because of injury to the most anterior part of the optic radiation, Meyer's loop. Diffusion tensor tractography is a promising technique for visualizing the optic radiation preoperatively. The aim of this study was to assess the anatomical accuracy of Meyer's loop, visualized by the two most common tractography methods­deterministic (DTG) and probabilistic tractography (PTG)­in patients who had undergone temporal lobe resection. METHODS: Eight patients with temporal lobe resection for temporal lobe pathology were included. Perimetry and diffusion tensor imaging were performed pre- and postoperatively. Two independent operators analyzed the distance between the temporal pole and Meyer's loop (TP-ML) using DTG and PTG. Results were compared to each other, to data from previously published dissection studies and to postoperative perimetry results. For the latter, Spearman's rank correlation coefficient (r(s)) was used. RESULTS: Median preoperative TP-ML distances for nonoperated sides were 42 and 35 mm, as determined by DTG and PTG, respectively. TP-ML assessed with PTG was a closer match to dissection studies. Intraclass correlation coefficients were 0.4 for DTG and 0.7 for PTG. Difference between preoperative TP-ML (by DTG and PTG, respectively) and resection length could predict the degree of postoperative visual field defects (DTG: r(s) = -0.86, p < 0.05; PTG: r(s) = -0.76, p < 0.05). CONCLUSION: Both DTG and PTG could predict the degree of visual field defects. However, PTG was superior to DTG in terms of reproducibility and anatomical accuracy. PTG is thus a strong candidate for presurgical planning of temporal lobe resection that aims to minimize injury to Meyer's loop.

Tumour size measurement in a mouse model using high resolution MRI.

BACKGROUND: Animal models are frequently used to assess new treatment methods in cancer research. MRI offers a non-invasive in vivo monitoring of tumour tissue and thus allows longitudinal measurements of treatment effects, without the need for large cohorts of animals. Tumour size is an important biomarker of the disease development, but to our knowledge, MRI based size measurements have not yet been verified for small tumours (10-2-10-1 g). The aim of this study was to assess the accuracy of MRI based tumour size measurements of small tumours on mice. METHODS: 2D and 3D T2-weighted RARE images of tumour bearing mice were acquired in vivo using a 7 T dedicated animal MR system. For the 3D images the acquired image resolution was varied. The images were exported to a PC workstation where the tumour mass was determined assuming a density of 1 g/cm(3), using an in-house developed tool for segmentation and delineation. The resulting data were compared to the weight of the resected tumours after sacrifice of the animal using regression analysis. RESULTS: Strong correlations were demonstrated between MRI- and necropsy determined masses. In general, 3D acquisition was not a prerequisite for high accuracy. However, it was slightly more accurate than 2D when small (<0.2 g) tumours were assessed for inter- and intraobserver variation. In 3D images, the voxel sizes could be increased from 1603 µm(3) to 2403 µm(3) without affecting the results significantly, thus reducing acquisition time substantially. CONCLUSIONS: 2D MRI was sufficient for accurate tumour size measurement, except for small tumours (<0.2 g) where 3D acquisition was necessary to reduce interobserver variation. Acquisition times between 15 and 50 minutes, depending on tumour size, were sufficient for accurate tumour volume measurement. Hence, it is possible to include further MR investigations of the tumour, such as tissue perfusion, diffusion or metabolic composition in the same MR session.

31P MR spectroscopy to evaluate the efficacy of hepatic artery embolization in the treatment of neuroendocrine liver metastases.

BACKGROUND: It is common to treat patients with metastatic disease from gastrointestinal neuroendocrine (NE) tumors with surgical reduction to prolong survival. This can be combined with hepatic arterial embolization (HAE) and medical treatment to reduce hormonal symptoms. Today there are no rapid and reliable methods to evaluate the efficacy of HAE in the treatment of neuroendocrine liver metastasis. PURPOSE: To investigate metabolic changes in hepatic metastases of NE tumors following HAE, and to establish if there are any early spectral patterns that might indicate therapeutic efficacy based on in vivo (31)P MRS data. MATERIAL AND METHODS: Volume selective (31)P MRS was used to study 11 patients with disseminated NE tumors with regional lymph nodes and bilobar liver metastases. Measurements were performed before and 1 and 3 days after HAE. RESULTS: Non-responders had significantly higher PME/Pi and αNTP/ΣNTP ratios than the responders before HAE (P < 0.05). Three days after HAE, non-responders still had significantly higher αNTP/ΣNTP than the responders did (P < 0.05). We also observed trends for increased PME ratios 3 days after HAE, decreased ATP-levels, and liberated Pi in responders. CONCLUSION: This (31)P-MRS study showed significant differences in PME/Pi and αNTP/ΣP ratios between responders and non-responders on the day before HAE, which is an interesting finding that may reflect intrinsic properties of the tumor tissue. We also observed trends for cell membrane renewal and increased energy consumption in responders after HAE. These results demonstrate potentials for (31)P-MRS to predict individual responsiveness prior to HAE.

Degraded water suppression in small volume ¹H MRS due to localised shimming.

OBJECT: High quality, artifact free, ¹H MRS require a homogeneous magnetic field over the volume of interest (VOI) and an effective global water suppression (WS). However, the shim coils act globally and, hence, affect the resonance frequency over the entire object, making the frequency selective WS spatially selective. Unsuppressed water signal may cause spurious echo artifacts. AIM: Study and visualise the effect localised shimming has on WS. MATERIALS AND METHODS: A water suppression imaging (WSI) scan for visualising regions unaffected by the WS was designed and applied in vivo for two different VOI localisations, at two field strengths. Two shim optimisation methods, and first and second order shims were compared. In addition, shim settings for six VOI localisations were retrospectively investigated. RESULTS: The WSI-scan effectively visualised the spatial extent of the WS. The coverage decreased when the shim was optimised on a smaller VOI. Second order shims accentuated the problem, resulting, on average, in a WS coverage of only 35% of the head volume. CONCLUSION: Localised shimming can result in large regions of unsuppressed water, which can lead to spurious echo artifacts in the spectrum. To help overcome these problems globally optimised shims can be used during WS.

Longitudinal study of the diffusion tensor imaging properties of the corpus callosum in acute and chronic diffuse axonal injury.

BACKGROUND: Magnetic resonance diffusion tensor imaging (MR-DTI) is used increasingly to detect diffuse axonal injury (DAI) after traumatic brain injury (TBI). PRIMARY OBJECTIVE: The primary objective was to investigate the changes in the diffusion properties of the corpus callosum in the acute phase and 6 months after TBI and to examine the correlation between DTI parameters and clinical outcome. RESEARCH DESIGN: Longitudinal prospective study. METHODS AND PROCEDURES: MR-DTI was performed in eight patients with suspected DAI within 11 days and at 6 months post-injury. Six controls were also examined. Fractional anisotropy (FA), trace and parallel and perpendicular diffusivity of the corpus callosum were analysed. The main outcome was the extended Glasgow Outcome Scale score, assessed at 6 months. MAIN OUTCOMES AND RESULTS: A significant reduction in FA in the corpus callosum was seen in the acute phase in patients compared with the healthy controls. There was no significant change in the parallel or perpendicular eigenvalues or trace. At 6 months, a significant reduction in FA and a significant increase in trace and perpendicular eigenvalues were noticed compared with controls. CONCLUSIONS: The diffusion properties of the corpus callosum correlated with clinical outcome in this longitudinal investigation.