Dynamic contrast-enhanced MRI using macromolecular contrast media for monitoring the response to isolated limb perfusion in experimental soft-tissue sarcomas

The objective of this study was to evaluate the potential of dynamic contrast-enhanced MRI for quantitative characterization of tumor microvessels and to assess the microvascular changes in response to isolated limb perfusion with TNF- and melphalan. Dynamic contrast-enhanced MRI was performed in an experimental cancer model, using a macromolecular contrast medium, albumin-(Gd-DTPA)₄₅. Small fragments of BN 175, a soft-tissue sarcoma, were implanted in 11 brown Norway (BN) rats. Animals were assigned randomly to a control (Haemaccel) or drug-treated group (TNF-/melphalan). MRI was performed at baseline and 24 h after ILP. The transendothelial permeability (K^PS) and the fractional plasma volume (fPV) were estimated from the kinetic analysis of MR data using a two-compartment bi-directional model. K^PS and fPV decreased significantly in the drug-treated group compared to baseline (p<0.05). In addition, K^PS post therapy was significantly lower (p<0.05) in the drug-treated group than in the control group. There was no significant difference in fPV between the drug-treated and the control group after therapy. Tumor microvascular changes in response to isolated limb perfusion can be determined after 24 h by dynamic contrast-enhanced MRI. The data obtained in this experimental model suggest possible applications in the clinical setting, using the appropriate MR contrast agents.     

Cervical carcinoma: standard and pharmacokinetic analysis of time-intensity curves for assessment of tumor angiogenesis and patient survival

Since detailed knowledge regarding the pathophysiological properties—which in turn are responsible for differences in contrast enhancement—remain fairly undetermined, it was the aim of this study (i) to examine the association of standard and pharmacokinetic analysis of time-intensity curves in dynamic MRI with histomorphological markers of tumor angiogenesis (microvessel density [MVD]; vascular endothelial growth factor [VEGF]) and (ii) to determine the ultimate value of a histomorphological and a dynamic MRI approach by correlation of those data with disease outcome in patients with primary cancer of the uterine cervix. Pharmacokinetic parameters (amplitude A, exchange rate constantk ₂₁) and standard parameters (maximum signal intensity (SI)-increase, [SI-I] over baseline and steepest SI-upslope, per second [SI-U/s]) were calculated from contrast-enhanced dynamic MR imaging series in 37 patients with biopsy-proven primary cervical cancer. On the surgical whole mount specimens, histomorphological markers of tumor angiogenesis (MVD, VEGF) were compared with similar sized and positioned regions-of-interest (ROIs) on the MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using log-rank statistics. A significant association was found betweenMVD and amplitudeA (P<0.01) andSI-I (P<0.05). No significant relationships were observed between theVEGF expression and all dynamic MRI parameters. Kaplan-Meier curves based onk ₂₁ and SI-U/s showed that tumors with highk ₂₁ andSI-U/s values had a significantly (P<0.05, 0.001, respectively) worse disease outcome than tumors with lowk ₂₁ andSI-U/s values. None of the histomorphological gold standard markers for assessing tumor angiogenesis (MVD, VEGF) had any significant power to predict patient survival. It is concluded that (1) the pathophysiological basis for differences in dynamic MRI isMVD but not VEGF-expression; (2) a functional, dynamic MRI approach (both standard and a pharmacokinetic analysis) may be better suited to assess angiogenic activity in terms of patient survival than current histomorphological-based markers of tumor angiogenesis; and [3] compared with standard analysis, a simple pharmacokinetic analysis of time-intensity curves is not superior to assessMVD or patient survival.     

Contrast enhancement in atherosclerosis development in a mouse model: in vivo results at 2 Tesla

To develop an MRI method for the evaluation of contrast enhancement in early atherosclerotic plaque development in the abdominal aorta of a mouse model. Male apoE^–/– mice from three groups, respectively 4 (n = 6), 8 (n = 11) and 16 (n = 4) weeks were included. Axial T1 spin echo images of the abdominal aorta were obtained above and below the renal arteries (90 m spatial resolution) before and over 1 h after the injection of a macromolecular contrast agent. Signal enhancement was measured in the vessel wall and compared to histological features. Maximal arterial wall signal enhancement was obtained from 16 to 32 min post injection. During this time, the signal-to-noise ratio increased by a factor up to 1.7 in 16 week mice and 2.7 and 2.4 in 8 and 4 weeks mice, respectively. The enhancement of the arterial wall appeared less pronounced in the oldest mice, 16 weeks old, exhibiting more advanced lesions. Using a macromolecular gadolinium agent, contrast uptake in atherogenesis varies with lesion stage and may be related to vessel-wall permeability. Dynamic contrast-enhanced MRI may be useful to evaluate the atherosclerotic plaque activity in mice.     

Benign prostate hyperplasia: evaluation of treatment response with DCE MRI

Benign prostate hyperplasia (BPH) is a major disease and its non-surgical therapy a major area of interest. The purpose of this study was to establish perfusion parameters in beagles with BPH using dynamic contrast-enhanced (DCE) MRI and to investigate changes due to the effects of finasteride treatment. Twelve male beagles (mean age 4.4±0.9,years) were divided into a control and treatment group that received a daily dose of 1 mg/kg finasteride. DCE MRI was carried out in a clinical scanner using a 3D spoiled gradient echo sequence prior to and during treatment. 0.2 mmol/kg contrast agent (gadoteridol) was administered with an injection rate of 0.2 ml/s followed by a 15 ml flush of saline. Contrast enhancement was evaluated by pharmacokinetic mapping of a two-compartment model with colour overlay images in addition to regional ROI analysis. Quantitative parameters were defined by the amplitude of contrast enhancement A, the exchange rate k_ep and the time to maximum signal enhancement. Dynamic contrast-enhanced MRI investigations of the prostate revealed two distinct zones, an inner, periurethral zone and an outer, parenchymal zone. The periurethral zone is highly vascularized, whereas the parenchymal zone is moderately vascularized when compared to other parenchymal organs. During treatment, in the parenchymal zone the intensity of enhancement (amplitude A) and the time to maximum signal enhancement increased, while the exchange rate k_ep decreased. Dynamic contrast-enhanced MRI of BPH reveals distinct differences between individual zones within the prostate. Moreover, changes during successful treatment suggest increased blood volume per volume of tissue and decreased vessel leakiness.     

Multi-Slice DCE-MRI Data Using P760 Distinguishes Between Metastatic and Non-Metastatic Rodent Prostate Tumors

An intermediate molecular weight contrast agent P760 was used to investigate the ability of multi-slice dynamic contrast-enhanced MRI (DCE-MRI) to distinguish metastatic from non-metastatic rodent prostate tumors. Non-metastatic AT2.1 and metastatic AT3.1 prostate tumors originally derived from the Dunning prostate cancer model were implanted on the hind leg of Copenhagen rats. Multi-sliced DCE-MRI data were acquired on a SIGNA 1.5 T scanner and analyzed using a recently developed empirical mathematical model. The P760 multi-slice DCE-MRI data in combination with the empirical mathematical model successfully distinguished between metastatic and non-metastatic rodent prostate tumors. Specifically, fitting the data with the empirical model showed that metastatic tumors had significantly faster contrast media uptake (p<0.001) and slower washout rates (p<0.01) than non-metastatic tumors     

Rat cerebral ischemia induced with photochemical occlusion of proximal middle cerebral artery: a stroke model for MR imaging research

A stroke model in rats with photochemically induced thrombosis (PIT) of proximal cerebral middle artery (MCA) is introduced for magnetic resonance imaging (MRI) study. Thirty-seven rats subjected to surgical and optical procedures for inducing the PIT models were scanned using a 1.5-T scanner with T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and contrast-enhanced perfusion-weighted imaging (PWI) at 1 h and 24 h after MCA occlusion. The penumbra evolution and PWI-derived parameters including relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) were monitored; and the relative lesion size (RLS) was compared with the final RLS on the gold standard triphenyl tetrazolium chloride (TTC) staining at 24 h. The results showed that the focal cerebral ischemic lesions were detectable in all rats with different MR approaches. The lesion on PWI at 1 h and on all MR images at 24 h was matched well with that seen on TTC staining; the peri-infarct area decreased from 6.2 ± 7.2% of the brain volume at 1 h to 0.3 ± 5.6% at 24 h. Compared to that in the contralateral hemisphere, rCBV in ischemic region was 52.6 ± 21.4 and 40.0 ± 15.8% (p > 0.05), and rCBF was 64.6 ± 11.2 and 47.3 ± 11.1% (p < 0.05) at 1 h and 24 h respectively. The present PIT model in rats has been successfully adopted for MRI research, which might be feasible for certain stroke studies and should be beneficial for the evaluation on effects of potential diagnostic and therapeutic approaches.     

Early changes in apparent diffusion coefficient of rat brain following total circulatory arrest

The apparent diffusion coefficient (ADC) of rat brain was determined for the cortex [(771±23)×10^–6 m²/s] and caudate-putamen (CP) [(601±25)×10^–6 m²/s]. Using the ultrafast imaging technique U-FLARE changes in ADC were followed with a 2.4-min temporal resolution after the induction of total circulatory arrest by intravenous KC1 injection. For both tissue types, a biphasic decrease of ADC was observed. The initial fast phase led to an ADC decrease by (27±4)% (cortex) and (29±3)% (CP) within 5 min, whereas the slow continuous decrease of the second phase resulted in (68±3)% (cortex) and (66±3)% (CP) of control after 18 min. The similar relative reduction in ADC for the cortex and the CP meant that an effective distinction between both tissue types persisted after the cessation of systemic and cerebral blood flow.Address for correspondence: Max-Planck Institut für neurologische Forschung, Gleuelerstrasse 50, D-50931 Köln, Germany. Additional reprints of this chapter may be obtained from the Reprints Department, Chapman & Hall, One Venn Plaza, New York, NY 10119.     

Short-echo-time magnetic resonance phase-shift velocity mapping for assessment of heart valve and great vessel stenoses: three years' experience

Shortening the echo times of magnetic resonance (MR) sequences used for phase-shift velocity mapping to 3.6 ms has extended use of the technique to measurement of velocities in turbulent, poststenotic jet flows. We used a 0.5-T MR machine and field even-echo rephasing (FEER) sequences with 3.6 ms echo times for jet velocity mapping.In vitro trials used continuous flow through a phantom with a 6-mm stenosis. Fifteen patients with mitral and/or aortic valve stenosis and 20 patients with repaired aortic coarctation were studied prospectively, with Doppler ultrasonic measurement of peak jet velocity performed independently on the same day. The clinical contribution of MR jet velocity mapping, used during a 3-year period in 306 patients with congenital and acquired disease of heart valves, great vessels, and conduits, was assessed retrospectively. The 3.6-ms sequence allowed accurate measurement of jet velocities up to 6 m s^–1 in vitro (r=0.996). Prospective studies in patients showed good agreement between MR and Doppler measurements of peak velocity:n=38; range, 1.2–6.1 m s^–1; mean, 2.7 m s^–1; mean of differences (Doppler-MR), 0.22 ms^–1; standard deviation of differences, ±0.38 m s^–1 (±14%). MR jet velocity mapping proved particularly valuable for assessment and localization of stenoses at sites where ultrasonic access was limited. The technique represents a diagnostic advance which can obviate the need for catheterization in selected cases.     

Proton MRS studies in Huntington's disease

We studied six patients in the early stage of Huntington's disease, together with six unaffected normal subjects. Localized spectra were acquired from 4-ml voxels encompassing the combined putamen and caudate head using STEAM with TR=1 s and TE=40 ms. Metabolite concentrations were calculated using tissue water as an internal reference. Although MRI showed minor degenerative changes in the basal ganglia, we were unable to detect any differences in the neuronal marker,N-acetylaspartate, between the two groups (patient mean ± SD, 10.7±2.1 µmol g wet wt^–1; controls 11.4±1.3). Similarly, we were unable to detect differences in either choline or creatine. In contrast to other studies, we were unable to detect any increase in lactate content of the basal ganglia in these patients with early stage disease. We conclude that proton MR spectroscopy will not be a suitable technique to detect the very early changes in asymptomatic patients identified as having the mutation.     

Prediction of pathological tumor volume in clinically localized prostate cancer: value of endorectal coil magnetic resonance imaging

The purpose of this study was to determine whether endorectal coil magnetic resonance imaging (MRI) enables accurate assessment of pathologic tumor volume in patients with clinically localized prostate carcinoma. Twenty-four patients with biopsy-proved prostate carcinoma underwent MRI at 0.5 T before radical prostatectomy. Tumor volumes were determined independently on axial fast-spin-echo (SE) T₂-weighted MR images and whole-mount pathology slides of the surgical specimens. At pathology, tumor volumes ranged from 0.17 to 9.42 cm³ (mean±SD, 3.11±2.99 cm³). A strong correlation (r=.944) was found between measurements of tumor volume based on MR images and pathological specimens. The error was less than 0.5 cm³ in 14 cases, in the range of 0.5–1 cm³ in 7 cases, and more than 1 cm³ in 3 cases. By using an MR tumor volume of 2 cm³ as cutoff value, extracapsular tumor spread could be predicted with a sensitivity of 81.2%, a specificity of 100%, and an accuracy of 87.5%. Tumor volume determinations based on MR images seem to be accurate enough to be helpful in clinical decision-making.     

Dynamic snapshot gradient-echo imaging of head and neck malignancies: time dependency and quality of contrast-to-noise ratio

The purpose of this study was to evaluate the time dependency of the contrast-to-noise ratio (CNR) of head and neck malignancies during contrast-enhanced MR imaging. Then we would compare the CNR of dynamic snapshot gradient-echo (SGE) images with conventional spin-echo (SE) and fast spin-echo (FSE) sequences. Fifteen patients with squamous cell carcinomas were examined with T1W-SE, T2W-FSE, contrast-enhanced Gd-TlW-SE, and T1W-SGE sequences, the latter statically and contrast-enhanced dynamically. The CNR for all sequences and adjacent tissues was computed and the time to reach maximal CNR (T_max) was determined for dynamic studies. The CNR was time dependent with two distinct T_max at 6–18 and 60–160 s which corresponded to two different tumor enhancement patterns. Neither enhancement pattern correlated with distinct histologic findings or tumor grading. The CNR improved for the Gd-TlW-SGE images. The improvement was statistically significant in relation to T1W-SE and Gd-TlW-SE images at the floor of the mouth and at the tongue base. The good CNR of the dynamic Gd-TlW-SGE measurements justifies further investigations of this method in order to improve tumor delineation.     

Characterization of Barium Titanate: BaTiO<Subscript>3</Subscript> (BT) Ceramics Prepared from Sol-Gel Derived BT Powders

Sol-gel synthesis was attempted at room temperature by adding drop wise a clear solution (made by reacting BaCO₃ with glacial acetic acid) to an equi-molar solution of titanium tetrabutoxide in isopropanol (IPA) and acetic acid. The gelation occurred within 30 minutes. The as-dried gel was calcined at 750^∘C/6 h in air to obtain carbon free BaTiO₃ powders. The resulting BT powders were further pressed into pellets and sintered at 1280^∘C/4 h in air to get dense ceramics (density ∼ 94%). XRD and SEM techniques were used for phase and microstructure analysis respectively. The room temperature relative permittivity (ε) of 1280 increased to 7200 (at Curie temperature of 127^∘C) at 1 kHz frequency. The dissipation factor (tanδ) ∼1.6% was observed in these samples. Also, the ferroelectric properties such as spontaneous polarization (Ps ∼ 13 μC/cm²), coercive field (E_c∼4.0 kV/cm) and dielectric strength (∼34 kV/cm) are estimated for these samples. These performance parameters are compared with the available standard data from the literature.     

Assignment of the 2.03 ppm resonance in in vivo <Superscript>1</Superscript>H MRS of human brain tumour cystic fluid: contribution of macromolecules

MRI and MRS are established techniques for the evaluation of intracranial mass lesions and cysts. The 2.03 ppm signal recorded in their ¹H-MRS spectra is often assigned to NAA from outer volume contamination, although it has also been detected in non-infiltrating tumours and large cysts. We have investigated the molecular origin of this resonance in ten samples of cystic fluids from human brain tumours. The NMR detected content of the 2.03 ppm resonance in 136 ms echo time spectra, assuming an N- CH₃ origin, was 3.19 ± 1.01 mM. Only one third (34 ± 12%) of the N-acetyl containing compound (NAC) signal could be extracted by perchloric acid (PCA) indicating that most of it originated in a macromolecular PCA-insoluble component. Chemical analysis of the cyst fluids showed that sialic acid bound to macromolecules would account for 64.3% and hexuronic containing compounds for 29.2% of the NMR-detectable ex vivo signal, 93.4% of the signal at TE 136 ms. Lactate content measured by NMR (6.4 ± 4.4 mM) and the predominance of NAC originating in sialic acid point to a major origin from tumour rather than from plasma for this 2.03 ppm resonance.     

Quantification of metabolites from single-voxelin vivo 1H NMR data of normal human brain by means of time-domain data analysis

We present here a combination of time-domain signal analysis procedures for quantification of human brainin vivo ¹H NMR spectroscopy (MRS) data. The method is based on a separate removal of a residual water resonance followed by a frequency-selective time-domain line-shape fitting analysis of metabolite signals. Calculation of absolute metabolite concentrations was based on the internal water concentration as a reference. The estimated average metabolite concentrations acquired from six regions of normal human brain with a single-voxel spin-echo technique for theN-acetylaspartate, creatine, and choline-containing compounds were 11.4±1.0,6.5±0.5, and 1.7±0.2 mmol kg^–1 wet weight, respectively. The time-domain analyses ofin vivo ¹H MRS data from different brain regions with their specific characteristics demonstrate a case in which the use of frequency-domain methods pose serious difficulties.     

Magnetic resonance imaging of coronary arteries and coronary stenosis

Coronary artery imaging is an important investigation for the management of coronary artery disease. Alternative noninvasive imaging would be useful, but the small caliber and tortuosity of the coronary vessels and cardiac and respiratory motion create formidable imaging problems. We first studied 21 normal subjects and 5 with coronary artery disease established by X-ray contrast angiography, of whom 2 had undergone bypass grafting. Of these, 22 were imaged successfully. Identification of the artery was possible for the left main stem, left anterior descending, right coronary, and left circumflex arteries respectively in 95%, 91%, 95%, and 76%. The arterial diameter at the origin could be measured in 77%, 77%, 81%, and 63%. The mean ±SD arterial diameter in each case (4.8±0.8, 3.7±0.5, 3.9±0.9, and 2.9±0.6 mm) was not significantly different from reference values (allp=ns). The mean length of artery visualized was 10.4±5.2,46.7±22.8,53.7±27.9, and 26.3±17.5 mm. In 12 normal males, the total coronary area was 30.9±9.2 mm² and the ratio compared with body surface area was 16.4±4.4 mm² m^–2 (bothp=ns compared with reference values). In seven patients, with X-ray contrast coronary angiography, the proximal arterial diameter measured by magnetic resonance was 3.9±1.1 mm, and by X-ray contrast angiography 3.7±1.0 mm (p=ns). We then studied 17 patients with angina. Imaging of just the relevant artery was performed and analysis was blinded to the X-ray angiography results. Stenosis was identified on the magnetic resonance (MR) images by localized reduction in vessel signal intensity. Stenosis location by MR was assessed by measurement of its distance from a reference vessel, with correlation to the X-ray findings. X-ray coronary angiography showed 23 stenoses of which 15 (65%) were correctly located by blind assessment of the MR images. Of the eight remaining stenoses, a further 5 (63%) were correctly located on the MR images after retrospective comparison (overall sensitivity 87%). There were three lesions thought to represent stenosis by MR, which on review of the X-ray angiogram proved to be a minor stenosis <50% (two cases) or a tortuous vessel (one case). Greater signal loss was seen in the more severe stenoses. The stenosis length by MRI was greater than by X-ray (8.4 versus 5.1 mm,p<0.001). The overestimation of stenosis length may be due to turbulence.     

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

Objective

To assess alterations in perfusion and liver function in the concanavalin A (ConA)-induced mouse model of acute liver failure (ALF) using two magnetic resonance imaging (MRI)-based methods: dynamic contrast-enhanced MRI (DCE-MRI) with Gd-EOB-DTPA contrast agent and arterial spin labelling (ASL).

Materials and methods

BALB/c mice were studied using a 9.4 T MRI system. The IntraGateFLASH^TM and FAIR-EPI pulse sequences were used for optimum mouse abdomen imaging.

Results

The average perfusion values for the liver of the control and ConA group were equal to 245 ± 20 and 200 ± 32 ml/min/100 g (p = 0.008, respectively). DCE-MRI showed that the time to the peak of the image enhancement was 6.14 ± 1.07 min and 9.72 ± 1.69 min in the control and ConA group (p < 0.001, respectively), while the rate of the contrast wash-out in the control and ConA group was 0.037 ± 0.008 and 0.021 ± 0.008 min^?1 (p = 0.004, respectively). These results were consistent with hepatocyte injury in the ConA-treated mice as confirmed by histopathological staining.

Conclusions

Both the ASL and DCE-MRI techniques represent a reliable methodology to assess alterations in liver perfusion and hepatocyte integrity in murine hepatitis.

     

Quantitative assessment of regional myocardial function in a rat model of myocardial infarction using tagged MRI

We characterized global and regional left ventricular (LV) function during post myocardium infarction (MI) remodeling in rats, which has been incompletely described by previous MRI studies. To assess regional wall motion, four groups of infarcted animals corresponding to 1–2, 3–4, 6–8 and 9–12 weeks post-MI respectively were imaged using a fast gradient echo sequence with a 2D spatial modulation of magnetization (SPAMM) tagging preparation. An additional group was serially imaged (1–2 and 6–7 weeks post-MI) to assess the global function. Regional and global functional parameters of infarcted rats were compared to non-infarcted normal rats. Compared to normal rats, a decrease in ejection fraction (70 ±7 vs. 40 ± 8%, p<0.05) was observed in rats with MI. Maximal and minimal principal stretches (₁, ₂) and strains (E₁, E₂), principal angle () and displacement varied regionally in normal rats but deviated significantly from the normal values in rats with MI particularly in the infarcted and adjacent zones. Not only was strain magnitude reduced segmentally post-MI, but strain direction became more circumferentially oriented, particularly in rats with larger infarctions. We report the first regional myocardial strain values in normal and infarcted rats. These results parallel findings in humans, and provide a unique tool to examine regional mechanical influences on the remodeling process.     

Specific targeting of folate–dendrimer MRI contrast agents to the high affinity folate receptor expressed in ovarian tumor xenografts

The need to develop target-specific MRI contrast agents to aid in disease characterization remains highly essential. In this study, we present a generation four polyamidoamine (PAMAM) folate-dendrimer that specifically targets the high affinity folate receptor (hFR) overexpressed on more than 80% of ovarian tumors. In vitro, mouse erythroleukemia cells expressing the hFR bind the radiolabeled folate-dendrimer chelate resulting in over 2700% increase in binding compared with untreated cells. The binding was inhibited by free folic acid to levels observed on folate-receptor-negative cells. In vivo, ovarian tumor xenografts resulted in a 33% contrast enhancement, following the folate-dendrimer chelate administration, that was significantly different compared with results obtained with a non-specific, extracellular fluid space agent, Gd-HP-DO3A. In addition, this contrast enhancement was absent in saline-treated animals, folate-receptor-negative tumors, and was inhibited by free folic acid. Results suggest that a macromolecular, dendrimeric MRI agent with high molecular relaxivities (1646 mM⁻¹ s⁻¹) can be used in specifically targeting the hFR on tumor cells and ovarian tumors.     

Dielectric and Ferroelectric Characterization of Na(Ta,Nb)O<Subscript>3</Subscript> Solid Solution Ceramics

Ceramics in the Na(Ta_{1 − x}Nb_x)O₃ system were prepared by a solid state reaction approach, and their dielectric characteristics were evaluated together with the structures. The complete solid solution with orthorhombic structures was observed in the present system, and three supposed phase transitions at about 475, 580 and 650^∘C were observed by DTA. Only one dielectric anomaly was observed at high temperature for x = 0.2 and 0.4, and alternative dielectric anomaly (a diffused dielectric peak) was observed around 170 and 380^∘C for x = 0.6 and 0.8, respectively. The compositions of 0.6 and 0.8 are weakly ferroelectric and those of 0.2 and 0.4 are supposed to be antiferroelectric at room temperature.     

Phase-based arterial input functions in humans applied to dynamic contrast-enhanced MRI: potential usefulness and limitations

Object  

Phase-based arterial input functions (AIFs) provide a promising alternative to standard magnitude-based AIFs, for example, because inflow effects are avoided. The usefulness of phase-based AIFs in clinical dynamic contrast-enhanced MRI (DCE-MRI) was investigated, and relevant pitfalls and sources of uncertainty were identified.