Rapid Progression of Autosomal Dominant Polycystic Kidney Disease: Urinary Biomarkers as Predictors.

BACKGROUND: Markers currently used to predict the likelihood of rapid disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) are expensive and time consuming to assess and often have limited sensitivity. New, easy-to-measure markers are therefore needed that alone or in combination with conventional risk markers can predict the rate of disease progression. In the present study, we investigated the ability of tubular damage and inflammation markers to predict kidney function decline. METHODS: At baseline, albumin, immunoglobulin G, kidney injury molecule 1, ß2 microglobulin (ß2MG), heart-type fatty acid-binding protein, neutrophil gelatinase-associated lipocalin, and monocyte chemotactic protein-1 -(MCP-1) were measured in 24-h urine samples of patients participating in a study investigating the therapeutic efficacy of lanreotide in ADPKD. Individual change in estimated glomerular filtration rate (eGFR) during follow-up was calculated using mixed-model analysis taking into account 13 -eGFRs (chronic kidney disease EPIdemiology) per patient. Logistic regression analysis was used to select urinary biomarkers that had the best association with rapidly progressive disease. The predictive value of these selected urinary biomarkers was compared to other risk scores using C-statistics. RESULTS: Included were 302 patients of whom 53.3% were female, with an average age of 48 ± 7 years, eGFR of 52 ± 12 mL/min/1.73 m2, and a height-adjusted total kidney volume (htTKV) of 1,082 (736-1,669) mL/m. At baseline, all urinary damage and inflammation markers were associated with baseline eGFR, also after adjustment for age, sex and baseline htTKV. For longitudinal analyses only patients randomized to standard care were considered (n = 152). A stepwise backward analysis revealed that ß2MG and MCP-1 showed the strongest association with rapidly progressive disease. A urinary biomarker score was created by summing the ranking of tertiles of ß2MG and MCP-1 excretion. The predictive value of this urinary biomarker score was higher compared to that of the Mayo htTKV classification (area under the curve [AUC] 0.73 [0.64-0.82] vs. 0.61 [0.51-0.71], p = 0.04) and comparable to that of the predicting renal outcomes in -ADPKD score (AUC 0.73 [0.64-0.82] vs. 0.65 [0.55-0.75], p = 0.18). In a second independent cohort with better kidney function, similar results were found for the urinary biomarker score. CONCLUSION: Measurement of urinary ß2MG and MCP-1 excretion allows selection of ADPKD patients with rapidly progressive disease, with a predictive value comparable to or even higher than that of TKV or PKD mutation. Easy and inexpensive to measure urinary markers therefore hold promise to help predict prognosis in ADPKD.

Polyuria due to vasopressin V2 receptor antagonism is not associated with increased ureter diameter in ADPKD patients.

BACKGROUND: Tolvaptan, a vasopressin V2 receptor antagonist, has been shown to reduce the rates of growth in total kidney volume (TKV) and renal function loss in ADPKD patients, but also leads to polyuria because of its aquaretic effect. Prolonged polyuria can result in ureter dilatation with consequently renal function loss. Therefore, we aimed to investigate the effect of tolvaptan-induced polyuria on ureter diameter in ADPKD patients. METHODS: 70 ADPKD patients were included (51 were randomized to tolvaptan and 19 to placebo). At baseline and after 3 years of treatment renal function was measured (mGFR) and MRI was performed to measure TKV and ureter diameter at the levels of renal pelvis and fifth lumbar vertebral body (L5). RESULTS: In these patients [65.7 % male, age 41 ± 9 years, mGFR 74 ± 27 mL/min/1.73 m2 and TKV 1.92 (1.27-2.67) L], no differences were found between tolvaptan and placebo-treated patients in 24-h urine volume at baseline (2.5 vs. 2.5 L, p = 0.8), nor in ureter diameter at renal pelvis and L5 (4.0 vs. 4.2 mm, p = 0.4 and 3.0 vs. 3.1 mm, p = 0.3). After 3 years of treatment 24-h urine volume was higher in tolvaptan-treated patients when compared to placebo (4.7 vs. 2.3 L, p < 0.001), but no differences were found in ureter diameter between both groups (renal pelvis: 4.2 vs. 4.4 mm, p = 0.4 and L5: 3.1 vs. 3.3 mm, p = 0.4). CONCLUSIONS: Tolvaptan-induced polyuria did not lead to an increase in ureter diameter, suggesting that tolvaptan is a safe therapy from a urological point of view.

Estimation of total kidney volume in autosomal dominant polycystic kidney disease.

BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD), obtaining measured total kidney volume (mTKV) by magnetic resonance (MR) imaging and manual tracing is time consuming. Two alternative MR imaging methods have recently been proposed to estimate TKV (eTKVellipsoid and eTKVPANK), which require less time. STUDY DESIGN: Cross-sectional and longitudinal diagnostic test study. SETTING & PARTICIPANTS: Patients with ADPKD with a wide range of kidney function and an approved T2-weighted MR image obtained at the University Medical Centers of Groningen, Leiden, Nijmegen, and Rotterdam, the Netherlands, in 2007 to 2014. Test set for assessing reproducibility, n=10; cohort for cross-sectional analyses, n=220; and cohort for longitudinal analyses, n=48. INDEX TESTS: Average times for eTKVellipsoid and eTKVPANK were 5 and 15 minutes, respectively. Bias is defined as (mTKV - eTKV)/mTKV × 100%; precision, as one standard deviation of bias. REFERENCE TESTS: mTKV using manual tracing to calculate the area within kidney boundaries times slice thickness. Average time for mTKV was 55 minutes. RESULTS: In the test set, intra- and intercoefficients of variation for mTKV, eTKVellipsoid, and eTKVPANK were 1.8% and 2.3%, 3.9% and 6.3%, and 3.0% and 3.4%, respectively. In cross-sectional analysis, baseline mTKV, eTKVellipsoid, and eTKVPANK were 1.96 (IQR, 1.28-2.82), 1.93 (IQR, 1.25-2.82), and 1.81 (IQR, 1.17-2.62) L, respectively. In cross-sectional analysis, bias was 0.02% ± 3.2%, 1.4% ± 9.2%, and 4.6% ± 7.6% for repeat mTKV, eTKVellipsoid, and eTKVPANK, respectively. In longitudinal analysis, no significant differences were observed between percentage change in mTKV (16.7% ± 17.1%) and percentage change in eTKVellipsoid (19.3% ± 16.1%) and eTKVPANK (17.8% ± 16.1%) over 3 years. LIMITATIONS: Results for follow-up data should be interpreted with caution because of the limited number of patients. CONCLUSIONS: Both methods for eTKV perform relatively well compared to mTKV and can detect change in TKV over time. Because eTKVellipsoid requires less time than eTKVPANK, we suggest that this method may be preferable in clinical care.

Short-term Effects of Tolvaptan in Individuals With Autosomal Dominant Polycystic Kidney Disease at Various Levels of Kidney Function.

BACKGROUND: A recent study showed that tolvaptan, a vasopressin V2 receptor antagonist, decreased total kidney volume (TKV) growth and estimated glomerular filtration rate (GFR) loss in autosomal dominant polycystic kidney disease (ADPKD) with creatinine clearance≥60mL/min. The aim of our study was to determine whether the renal hemodynamic effects and pharmacodynamic efficacy of tolvaptan in ADPKD are dependent on GFR. STUDY DESIGN: Clinical trial with comparisons before and after treatment. SETTING & PARTICIPANTS: Patients with ADPKD with a wide range of measured GFRs (mGFRs; 18-148 mL/min) in a hospital setting. INTERVENTION: Participants were studied at baseline and after 3 weeks of treatment with tolvaptan given in increasing dosages, if tolerated (doses of 60, 90, and 120mg/d in weeks 1, 2, and 3, respectively). OUTCOMES: Change in markers for aquaresis (free-water clearance, urine and plasma osmolality, 24-hour urine volume, and plasma copeptin) and kidney injury (TKV and kidney injury biomarkers). MEASUREMENTS: GFR was measured by (125)I-iothalamate clearance; TKV, by magnetic resonance imaging; biomarker excretion, by enzyme-linked immunosorbent assay; and osmolality, by freezing point depression. RESULTS: In 27 participants (52% men; aged 46±10 years; mGFR, 69±39mL/min; TKV, 2.15 [IQR, 1.10-2.77] L), treatment with tolvaptan led to an increase in urine volume and free-water clearance and a decrease in urine osmolality, TKV, and kidney injury marker excretion. Changes in urine volume and osmolality with treatment were less in participants with lower baseline mGFRs (both P<0.01). However, change in fractional free-water clearance was greater at lower baseline mGFRs (P=0.001), suggesting that participants with decreased GFRs responded more to tolvaptan per functioning nephron. LIMITATIONS: Limited sample size, no control group. CONCLUSIONS: In patients with ADPKD with decreased kidney function, response to tolvaptan is lower for TKV, urinary volume, and osmolality, but larger for fractional free-water clearance. This latter finding suggests that patients with ADPKD with lower GFRs might benefit from long-term treatment with tolvaptan, as has been observed for patients with preserved GFRs.

Rationale and design of the DIPAK 1 study: a randomized controlled clinical trial assessing the efficacy of lanreotide to Halt disease progression in autosomal dominant polycystic kidney disease.

BACKGROUND: There are limited therapeutic options to slow the progression of autosomal dominant polycystic kidney disease (ADPKD). Recent clinical studies indicate that somatostatin analogues are promising for treating polycystic liver disease and potentially also for the kidney phenotype. We report on the design of the DIPAK 1 (Developing Interventions to Halt Progression of ADPKD 1) Study, which will examine the efficacy of the somatostatin analogue lanreotide on preservation of kidney function in ADPKD. STUDY DESIGN: The DIPAK 1 Study is an investigator-driven, randomized, multicenter, controlled, clinical trial. SETTING & PARTICIPANTS: We plan to enroll 300 individuals with ADPKD and estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m(2) who are aged 18-60 years. INTERVENTION: Patients will be randomly assigned (1:1) to standard care or lanreotide, 120 mg, subcutaneously every 28 days for 120 weeks, in addition to standard care. OUTCOMES: Main study outcome is the slope through serial eGFR measurements starting at week 12 until end of treatment for lanreotide versus standard care. Secondary outcome parameters include change in eGFR from pretreatment versus 12 weeks after treatment cessation, change in kidney volume, change in liver volume, and change in quality of life. MEASUREMENTS: Blood and urine will be collected and questionnaires will be filled in following a fixed scheme. Magnetic resonance imaging will be performed for assessment of kidney and liver volume. RESULTS: Assuming an average change in eGFR of 5.2 ± 4.3 (SD) mL/min/1.73 m(2) per year in untreated patients, 150 patients are needed in each group to detect a 30% reduction in the rate of kidney function loss between treatment groups with 80% power, 2-sided α = 0.05, and 20% protocol violators and/or dropouts. LIMITATIONS: The design is an open randomized controlled trial and measurement of our primary end point does not begin at randomization. CONCLUSIONS: The DIPAK 1 Study will show whether subcutaneous administration of lanreotide every 4 weeks attenuates disease progression in patients with ADPKD.

MRI in patients with a cerebral aneurysm clip; review of the literature and incident databases and recommendations for the Netherlands.

BACKGROUND: In the past ferromagnetic cerebral aneurysm clips that are contraindicated for Magnetic Resonance Imaging (MRI) have been implanted. However, the specific clip model is often unknown for older clips, which poses a problem for individual patient management in clinical care. METHODS: Literature and incident databases were searched, and a survey was performed in the Netherlands that identified time periods at which ferromagnetic and non-ferromagnetic clip models were implanted. Considering this information in combination with a national expert opinion, we describe an approach for risk assessment prior to MRI examinations in patients with aneurysm clips. The manuscript is limited to MRI at 1.5 T or 3 T whole body MRI systems with a horizontal closed bore superconducting magnet, covering the majority of clinical Magnetic Resonance (MR) systems. RESULTS: From the literature a list of ferromagnetic clip models was obtained. The risk of movement or rotation of the clip due to the main magnetic field in case of a ferromagnetic clip is the main concern. In the incident databases records of four serious incidents due to aneurysm clips in MRI were found. The survey in the Netherlands showed that from 2000 onwards, no ferromagnetic clips were implanted in Dutch hospitals. DISCUSSION: Recommendations are provided to help the MR safety expert assessing the risks when a patient with a cerebral aneurysm clip is referred for MRI, both for known and unknown clip models. This work was part of the development of a guideline by the Dutch Association of Medical Specialists.

Effects of microperfusion in hepatic diffusion weighted imaging.

OBJECTIVE: Clinical hepatic diffusion weighted imaging (DWI) generally relies on mono-exponential diffusion. The aim was to demonstrate that mono-exponential diffusion in the liver is contaminated by microperfusion and that the bi-exponential model is required. METHODS: Nineteen fasting healthy volunteers were examined with DWI (seven b-values) using fat suppression and respiratory triggering (1.5 T). Five different regions in the liver were analysed regarding the mono-exponentially fitted apparent diffusion coefficient (ADC), and the bi-exponential model: molecular diffusion (D (slow)), microperfusion (D (fast)) and the respective fractions (f (slow/fast)). Data were compared using ANOVA and Kruskal-Wallis tests. Simulations were performed by repeating our data analyses, using just the DWI series acquired with b-values approximating those of previous studies. RESULTS: Median mono-exponentially fitted ADCs varied significantly (P < 0.001) between 1.107 and 1.423 × 10(-3) mm(2)/s for the five regions. Bi-exponential fitted D(slow) varied between 0.923 and 1.062 × 10(-3) mm(2)/s without significant differences (P = 0.140). D (fast) varied significantly, between 17.8 and 46.8 × 10(-3) mm(2)/s (P < 0.001). F-tests showed that the diffusion data fitted the bi-exponential model significantly better than the mono-exponential model (F > 21.4, P < 0.010). These results were confirmed by the simulations. CONCLUSION: ADCs of normal liver tissue are significantly dependent on the measurement location because of substantial microperfusion contamination; therefore the bi-exponential model should be used. KEY POINTS: Diffusion weighted MR imaging helps clinicians to differentiate tumours by diffusion properties. Fast moving water molecules experience microperfusion, slow molecules diffusion. Hepatic diffusion should be measured by bi-exponential models to avoid microperfusion contamination. Mono-exponential models are contaminated with microperfusion, resulting in apparent regional diffusion differences. Bi-exponential models are necessary to measure diffusion and microperfusion in the liver.

Determination of choline concentration in breast lesions: quantitative multivoxel proton MR spectroscopy as a promising noninvasive assessment tool to exclude benign lesions.

PURPOSE: To determine the optimal cutoff of choline (Cho) concentration in quantitative multivoxel magnetic resonance (MR) spectroscopic data to safely prove benignancy in breast lesions. MATERIALS AND METHODS: The study was institutional review board approved, and informed consent was obtained from each patient. Between July 2009 and July 2010, multivoxel MR spectroscopy was performed in 24 consecutive patients with 25 breast lesions assessed as Breast Imaging Reporting and Data System 3 or 4 and larger than 1 cm in diameter at mammography. Two-dimensional point-resolved spatially localized spectroscopy chemical shift imaging was first performed without signal suppression (repetition time msec/echo time msec, 1500/30) as reference measurement and was performed subsequently with suppression of water and fat signals (1500/135) to detect Cho. Differences in mean and highest Cho concentration in the breast lesions were tested for significance by using the independent sample t test. The final diagnosis was confirmed with pathologic findings. RESULTS: Fourteen of 25 breast lesions were malignant. The mean Cho concentration varied between 0.3 and 1.3 mmol/L (0.84 mmol/L ± 0.32 [standard deviation]) in benign lesions and between 1.3 and 9.5 mmol/L (3.10 mmol/L ± 2.21) in malignant lesions. The highest Cho concentrations in benign and malignant lesions were 0.4-1.5 mmol/L (1.19 mmol/L ± 0.33) and 1.7-11.8 mmol/L (4.08 mmol/L ± 2.81), respectively. Mean and highest Cho concentrations in benign and malignant breast lesions differed significantly (P = .02 for both). CONCLUSION: The study, in a relatively small patient population, shows that quantitative multivoxel MR spectroscopy can be applied to exclude benign breast lesions from further invasive diagnostic work-up with the implementation of a Cho concentration of 1.5 mmol/L or lower as a cutoff. Further larger studies will be needed to confirm these results.

Diffusion-weighted imaging of normal fibroglandular breast tissue: influence of microperfusion and fat suppression technique on the apparent diffusion coefficient.

The influence of microperfusion and fat suppression technique on the apparent diffusion coefficient (ADC) values obtained with diffusion weighted imaging (DWI) of normal fibroglandular breast tissue was investigated. Seven volunteers (14 breasts) were scanned using diffusion weighting factors (b values) up to 1600 s/mm(2) and the four different fat suppression techniques: STIR, fat saturation, SPAIR, and Water Excitation. The relationship between the logarithmic DW attenuation curves and b was linear for b values up to 600 s/mm(2) (R(2) > 0.999). Small differences were noted between the ADC values obtained with the various fat suppression methods, especially at the higher b values. Water Excitation had the highest mean SNR, exceeding STIR (p = 0.03) though not significantly different from fat saturation and SPAIR. In conclusion, the ADC of fibroglandular breast tissue is not influenced by microperfusion and Water Excitation is recommended because it yielded the best SNR values. These factors may be crucial in the differentiation between benign and malignant lesions.

T1 vs. T2 weighted magnetic resonance imaging to assess total kidney volume in patients with autosomal dominant polycystic kidney disease.

PURPOSE: In ADPKD patients total kidney volume (TKV) measurement using MRI is performed to predict rate of disease progression. Historically T1 weighted images (T1) were used, but the methodology of T2 weighted imaging (T2) has evolved. We compared the performance of both sequences. METHODS: 40 ADPKD patients underwent an abdominal MRI at baseline and follow-up. TKV was measured by manual tracing with Analyze Direct 11.0 software. Three readers established intra- and interreader coefficients of variation (CV). T1 and T2 measured kidney volumes and growth rates were compared with ICC and Bland-Altman analyses. RESULTS: Participants were 49.7 ± 7.0 years of age, 55.0% female, with estimated GFR of 50.1 ± 11.5 mL/min/1.73 m2. CVs were low and comparable for T2 and T1 (intrareader: 0.83% [0.48-1.79] vs. 1.15% [0.34-1.77], P = 0.9, interreader: 2.18% [1.59-2.61] vs. 1.69% [1.07-3.87], P = 0.9). TKV was clinically similar, but statistically significantly different between T2 and T1: 1867 [1172-2721] vs. 1932 [1180-2551] mL, respectively (P = 0.006), with a bias of only 0.8% and high agreement (ICC 0.997). Percentage kidney growth during 2.2 ± 0.3 years was similar for T2 and T1 (9.3 ± 10.6% vs. 7.8 ± 9.9%, P = 0.1, respectively), with a bias of 1.5% and high agreement (ICC 0.843). T2 was more often of sufficient quality for volume measurement (86.7% vs. 71.1%, P < 0.001). CONCLUSIONS: In patients with ADPKD, measurement of kidney volume and growth rate performs similarly when using T2 compared to T1 weighted images, although T2 performs better on secondary outcome parameters; they are more often of sufficient quality for volume measurement and result in slightly lower intra- and interreader variability.

Correlation between serum ferritin levels and liver iron concentration determined by MR imaging: impact of hematologic disease and inflammation.

Liver iron concentration was determined in 28 patients by magnetic resonance imaging using the method of Gandon et al. (Non-invasive assessment of hepatic iron stores by MRI. Lancet 2004;363:357-362). The result showed a significant correlation with blood plasma ferritin content (Spearman's r=.66; P<.001) and a slightly improving correlation coefficient when limited to those patients not known to have inflammation (r=.82; n=17; P<.001). Zooming in on patients with hematologic disease also had a beneficial effect on the correlation between liver iron content and plasma ferritin level (r=.79; n=13; P=.001). It is concluded that in patients without inflammation and in patients with hematologic disease, the content of ferritin in blood is a better predictor of liver iron content than in other patient categories.

Parallel imaging for first-pass myocardial perfusion.

Two parallel imaging methods used for first-pass myocardial perfusion imaging were compared in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and image artifacts. One used adaptive Time-adaptive SENSitivity Encoding (TSENSE) and the other used GeneRalized Autocalibrating Partially Parallel Acquisition (GRAPPA), which are both applied to a gradient-echo sequence. Both methods were tested on 12 patients with coronary artery disease. The order of perfusion sequences was inverted in every other patient. Image acquisition was started during the administration of a contrast bolus followed by a 20-ml saline flush (3 ml/s), and the next perfusion was started at least 15 min thereafter using an identical bolus. An acceleration rate of 2 was used in both methods, and acquisition was performed during breath-holding. Significantly higher SNR, CNR and image quality were obtained with GRAPPA images than with TSENSE images. GRAPPA, however, did not yield a higher CNR when applied after the second bolus. GRAPPA perfusion imaging produced larger differences between subjects than did TSENSE. Compared to TSENSE, GRAPPA produced significantly better CNR on the first bolus. More consistent SNR and CNR were obtained from TSENSE images than from GRAPPA images, indicating that the diagnostic value of TSENSE may be better.

Assessment of the link between quantitative biexponential diffusion-weighted imaging and contrast-enhanced MRI in the liver.

PURPOSE: To investigate if intravoxel incoherent motion (IVIM) modeled diffusion-weighted imaging (DWI) can be linked to contrast-enhanced (CE-)MRI in liver parenchyma and liver lesions. METHODS: Twenty-five patients underwent IVIM-DWI followed by multiphase CE-MRI using Gd-EOB-DTPA (n=20) or Gd-DOTA (n=5) concluded with IVIM-DWI. Diffusion (Dslow), microperfusion (Dfast), its fraction (ffast), wash-in-rate (Rearly) and late-enhancement-rate (Rlate) of Gd-EOB-DTPA were calculated voxel-wise for the liver. Parenchyma and lesions were segmented. Pre-contrast IVIM was compared 1) between low, medium and high Rearly for parenchyma 2) to post-contrast IVIM substantiated with simulations 3) between low and high Rlate per lesion type. RESULTS: Dfast and ffast increased (P<0.001) with 25.6% and 33.8% between low and high Rearly of Gd-EOB-DTPA. Dslow decreased (-15.0%; P<0.001) with increasing Rearly. Gd-DOTA demonstrated similar observations. ffast (+10%; P<0.001) and Dfast (+6.6%; P<0.001) increased after Gd-EOB-DTPA, while decreasing after Gd-DOTA (-4.2% and -5.7%, P<0.001) and were confirmed by simulations. For focal nodular hyperplasia lesions (n=5) Dfast and ffast increased (P<0.001) with increasing Rlate, whereas for hepatocellular carcinoma (n=4) and adenoma (n=7) no differences were found. CONCLUSION: Microperfusion measured by IVIM reflects perfusion in a way resembling CE-MRI. Also IVIM separated intra- and extracellular MR contrast media. This underlines the potential of IVIM in quantitative liver imaging.

Clinical implications of non-steatotic hepatic fat fractions on quantitative diffusion-weighted imaging of the liver.

Diffusion-weighted imaging (DWI) is an important diagnostic tool in the assessment of focal liver lesions and diffuse liver diseases such as cirrhosis and fibrosis. Quantitative DWI parameters such as molecular diffusion, microperfusion and their fractions, are known to be affected when hepatic fat fractions (HFF) are higher than 5.5% (steatosis). However, less is known about the effect on DWI for HFF in the normal non-steatotic range below 5.5%, which can be found in a large part of the population. The aim of this study was therefore to evaluate the diagnostic implications of non-steatotic HFF on quantitative DWI parameters in eight liver segments. For this purpose, eleven healthy volunteers (2 men, mean-age 31.0) were prospectively examined with DWI and three series of in-/out-of-phase dual-echo spoiled gradient-recalled MRI sequences to obtain the HFF and T2*. DWI data were analyzed using the intravoxel incoherent motion (IVIM) model. Four circular regions (ø22.3 mm) were drawn in each of eight liver segments and averaged. Measurements were divided in group 1 (HFF ≤ 2.75%), group 2 (2.75< HFF ≤ 5.5%) and group 3 (HFF>5.5%). DWI parameters and T2* were compared between the three groups and between the segments. It was observed that the molecular diffusion (0.85, 0.72 and 0.49 × 10(-3) mm(2)/s) and T2* (32.2, 27.2 and 21.0 ms) differed significantly between the three groups of increasing HFF (2.18, 3.50 and 19.91%). Microperfusion and its fraction remained similar for different HFF. Correlations with HFF were observed for the molecular diffusion (r = -0.514, p<0.001) and T2* (-0.714, p<0.001). Similar results were obtained for the majority of individual liver segments. It was concluded that fat significantly decreases molecular diffusion in the liver, also in absence of steatosis (HFF ≤ 5.5%). Also, it was confirmed that fat influences T2*. Determination of HFF prior to quantitative DWI is therefore crucial.

Quantitative multivoxel proton chemical shift imaging of the breast.

The study of focal pathology by single-voxel magnetic resonance spectroscopy (MRS) is hampered by the impossibility to study tissue heterogeneity or compare the metabolite signals in breast lesion directly to those in unaffected tissue. Multivoxel MRS studies, while potentially allowing for truly quantitative tissue characterization, have up to now also been far from quantitative with, for example, the signal-to-noise ratio of the choline (Cho) signal serving as measure of tumor activity. Shown in this study is that in a standard clinical setting with a regular 1.5-T magnetic resonance scanner, it is possible to perform quantitative multivoxel MRS. With the use of literature values for the T1 and T2 relaxation times of Cho and water in fibroglandular breast tissue and tumors, one can determine the concentrations of Cho in different tumor compartments and surrounding tissues in two brief multivoxel MRS measurements. This opens excellent perspectives to quantitative diagnostic and follow-up studies of focal pathology such as lesions suspected of breast cancer.

Non-invasive liver iron concentration measurement by MRI: comparison of two validated protocols.

In the non-invasive determination of the liver iron concentration several validated MRI methods are available, two of which are compared in this study. Twenty-eight patients were examined by MRI and evaluated by the methods of Kreeftenberg et al. [Kreeftenberg Jr HG, Mooyaart EL, Huizenga JR, Sluiter WJ, Kreeftenberg Sr HG. Quantification of liver iron concentration with magnetic resonance imaging by combining T1-, T2-weighted spin echo sequences and a gradient echo sequence. Neth J Med 2000;56:133-7] and Gandon et al. [Gandon Y, Olivie D, Guyader D, et al. Non-invasive assessment of hepatic iron stores by MRI. Lancet 2004;363:357-62]. It is concluded that the latter shows a better inter- and intra-observer correlation and is more accurate because of the automated preselection of one of five sequences most sensitive in the estimated liver iron concentration range. In the Kreeftenberg method combining the results of three suboptimal sequences, leads to underestimation of the liver iron concentration.

Multiple voxel 1H MR spectroscopy of phosphorylase-b kinase deficient patients (GSD IXa) showing an accumulation of fat in the liver that resolves with aging.

BACKGROUND/AIMS: Phosphorylase-b deficient patients suffer from glycogen storage disease (GSD IXa) leading to liver enlargement which usually resolves during puberty and adolescence. This pathology has not yet been documented by (1)H MR spectroscopy (MRS) investigation. METHODS: MRS of eight GSD IXa patients was performed in this study to assess whether or not liver fat content is elevated in GSD IXa and decreases with aging. An improvement in our MRS method compared with previous liver fat MRS studies is that we measured a plane of liver voxels at once rather than a single MRS voxel, yielding a reliable determination of liver fat content. RESULTS: Fat contents of 3.4-10% were observed in young GSD IXa patients, as compared with 0.5-0.9% in controls, these dropped to control levels in patients past age 40 (r = -0.82; P < 0.01). CONCLUSIONS: Liver fat content is increased in glycogen storage disease (GSD IXa) and normalizes with ageing. Assessing liver fat levels in this population is a novel and interesting concept. This could potentially enhance the understanding of liver function in that 20% of the population who has increased liver fat.