Dynamic contrast-enhanced MRI in advanced nonsmall-cell lung cancer patients treated with first-line bevacizumab, gemcitabine, and cisplatin

Purpose:

To investigate dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) of advanced nonsmall‐cell lung cancer (NSCLC) patients treated with the antiangiogenic agent bevacizumab combined with gemcitabine and cisplatin as first‐line treatment.

Materials and Methods:

All patients were enrolled for MRI and computed tomography (CT) before and after the first three courses of bevacizumab combination chemotherapy. Pharmacokinetic parameters (K^trans, k_ep, v_e, v_p) derived from DCE MRI were computed for the main mass. Parametric histogram analysis was obtained to evaluate changes of the internal tumor composition and for correlation with tumor response measured on CT.

Results:

After three cycles of treatment, 11 patients showed decreased tumor size and a decreased value of all MR‐derived pharmacokinetic parameters. Among these parameters, there was a significant decrease of mean and standard deviation of the K^trans histogram as well as a decrease of mean of the k_ep histogram (P < 0.05). Tumors with larger mean values of rate constant k_ep (P < 0.0001) and smaller standard deviation of volume of extravascular extracellular space fraction v_e (P < 0.0001) on histograms before chemotherapy were considered predictors for treatment response.

Conclusion:

DCE MRI enables a functional analysis of the treatment response of NSCLC. MRI parametric histogram has the potential to predict early treatment response of combined bevacizumab, gemcitabine, and cisplatin. J. Magn. Reson. Imaging 2012;36:387–396. ©2012 Wiley Periodicals, Inc.     

Model-based, semiquantitative and time intensity curve shape analysis of dynamic contrast-enhanced MRI: a comparison in patients undergoing antiangiogenic treatment for recurrent glioma

Purpose:

To compare time intensity curve (TIC)‐shape analysis of dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) data with model‐based analysis and semiquantitative analysis in patients with high‐grade glioma treated with the antiangiogenic drug bevacizumab.

Materials and Methods:

Fifteen patients had a pretreatment and at least one posttreatment DCE‐MRI. We applied a pixel‐by‐pixel TIC shape analysis, where TICs are classified into five different types according to their shape, and calculated the occurrence of each TIC type in the region of interest (ROI). The results were compared to the pharmacokinetic model (PKM) parameters K^trans, K_ep, V_e, and V_i, and with the semiquantitative parameters maximum enhancement (ME) and initial slope of increase (ISI).

Results:

The relative amount of type 2 and 4 TIC shape significantly correlated with the parameter K_ep but not with K^trans or V_e. The PKM parameter V_e and the semiquantitative parameters ME and ISI showed significant changes after treatment. None of the TIC shapes individually showed significant changes.

Conclusion:

The semiquantitative parameters ME and ISI are more sensitive to the effect of the bevacizumab than K^trans and V_e. The pixel‐by‐pixel TIC shape analysis parameters are not sensitive to the effect of bevacizumab, although they can be seen as surrogates for the PKM parameter K_ep. J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc.     

Correlation of perfusion parameters on dynamic contrast-enhanced MRI with prognostic factors and subtypes of breast cancers

Purpose:

To investigate whether a correlation exists between perfusion parameters obtained from dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) and prognostic factors or immunohistochemical subtypes of breast cancers.

Materials and Methods:

Quantitative parameters (K^trans, k_ep, and v_e) of 70 invasive ductal carcinomas were obtained using DCE‐MRI as a postprocessing procedure. Correlations between parameters and prognostic factors, including tumor size, axillary nodal status, histologic grade, nuclear grade, expression of estrogen receptor (ER), progesterone receptor (PR), Ki‐67, p53, bcl‐2, and human epidermal growth factor receptor 2 (HER2) and subtypes categorized as luminal (ER or PR‐positive), triple negative (ER or PR‐negative, HER2‐negative), and HER2 (ER and PR‐negative, HER2 overexpression) were analyzed.

Results:

Mean K^trans was higher in tumors with a high histologic grade than with a low histologic grade (P = 0.007), with a high nuclear grade than with a low nuclear grade (P = 0.002), and with ER negativity than ER positivity (P = 0.056). Mean k_ep was higher in tumors with a high histologic grade than with a low histologic grade (P = 0.005), with a high nuclear grade than with a low nuclear grade (P = 0.001), and with ER negativity than with ER positivity (P = 0.043). Mean v_e was lower in tumors with a high histologic grade than with a low histologic grade (P = 0.038) and with ER negativity than with ER positivity (P = 0.015). Triple‐negative cancers showed a higher mean k_ep than the luminal type (P = 0.015).

Conclusion:

Breast cancers with higher K^trans and k_ep, or lower v_e, had poor prognostic factors and were often of the triple‐negative subtype. J. Magn. Reson. Imaging 2012;36:145–151. © 2012 Wiley Periodicals, Inc.     

Measuring perfusion and permeability in renal cell carcinoma with dynamic contrast‐enhanced MRI: A pilot study

Purpose:

To retrospectively assess an improved quantitative methodology with separate assessment of perfusion and permeability for characterization of primary renal cell carcinoma (RCC) and monitoring antiangiogenic treatment.

Materials and Methods:

Fifteen RCC patients before surgery, 6 RCC patients before and after neoadjuvant antiangiogenic therapy, and 15 patients without renal disease underwent dynamic contrast‐enhanced (DCE)‐MRI of the kidney with integrated retrospective respiratory triggering and an individual arterial input function. Tracer kinetic analysis was performed with a two‐compartment‐filtration‐model for the kidney data and a two‐compartment‐exchange‐model for the tumor data, providing four independent parameters: the perfusion‐parameters plasma flow (F_P) and plasma volume (V_P), and the permeability‐parameters extraction flow (F_E) and extravascular‐extracellular volume (V_E).

Results:

In tumors F_P and F_E were significantly lower than in normal kidneys. Tracer kinetic analysis displayed hemodynamic alteration caused by vessel infiltration or necrosis. Papillary RCC could be differentiated from clear‐cell variants by a distinct perfusion pattern. In antiangiogenically treated RCC V_E was not significantly decreased, while the perfusion parameters V_P and F_P were significantly diminished.

Conclusion:

DCE‐MRI with integrated motion compensation enables evaluation of primary RCC and detects distinct perfusion patterns. Quantification with a two‐compartment‐exchange‐model produces a separate perfusion‐ and permeability characterization and may become a diagnostic tool to monitor antiangiogenic treatment. J. Magn. Reson. Imaging 2010; 31: 490–501. © 2010 Wiley‐Liss, Inc.     

Impact of nonrigid motion correction technique on pixel-wise pharmacokinetic analysis of free-breathing pulmonary dynamic contrast-enhanced MR imaging

Purpose:

To investigates the impact of nonrigid motion correction on pixel‐wise pharmacokinetic analysis of free‐breathing DCE‐MRI in patients with solitary pulmonary nodules (SPNs). Misalignment of focal lesions due to respiratory motion in free‐breathing dynamic contrast‐enhanced MRI (DCE‐MRI) precludes obtaining reliable time–intensity curves, which are crucial for pharmacokinetic analysis for tissue characterization.

Materials and Methods:

Single‐slice 2D DCE‐MRI was obtained in 15 patients. Misalignments of SPNs were corrected using nonrigid B‐spline image registration. Pixel‐wise pharmacokinetic parameters K^trans, v_e, and k_ep were estimated from both original and motion‐corrected DCE‐MRI by fitting the two‐compartment pharmacokinetic model to the time–intensity curve obtained in each pixel. The “goodness‐of‐fit” was tested with χ²‐test in pixel‐by‐pixel basis to evaluate the reliability of the parameters. The percentages of reliable pixels within the SPNs were compared between the original and motion‐corrected DCE‐MRI. In addition, the parameters obtained from benign and malignant SPNs were compared.

Results:

The percentage of reliable pixels in the motion‐corrected DCE‐MRI was significantly larger than the original DCE‐MRI (P = 4 × 10^?7). Both K^trans and k_ep derived from the motion‐corrected DCE‐MRI showed significant differences between benign and malignant SPNs (P = 0.024, 0.015).

Conclusion:

The study demonstrated the impact of nonrigid motion correction technique on pixel‐wise pharmacokinetic analysis of free‐breathing DCE‐MRI in SPNs. J. Magn. Reson. Imaging 2011;33:968–973. © 2011 Wiley‐Liss, Inc.

     

Heuristic linear mapping of physiological parameters in dynamic contrast-enhanced MRI without T₁ measurement and contrast agent concentration

Purpose:

To present a novel heuristic linear mapping method to individually estimate physiological parameters for Tofts model without T₁ measurement and contrast agent concentration.

Materials and Methods:

A linear relationship was used for k_ep mapping through a heuristic time intensity curve (TIC) shape factor (TSF). K^trans maps were subsequently estimated using k_ep maps and another approximate linear model derived from the Tofts model. Twenty‐seven patients with head‐and‐neck squamous cell carcinoma received dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI). Physiological parameters maps were obtained using this heuristic linear mapping method and compared to the maps obtained by the normal nonlinear least‐square fitting with T₁ measurement.

Results:

High linearity (R² >0.95) between k_ep and TSF was found in all patients for k_ep <5/min. This linearity is robust for TSF timepoint selection. The k_ep maps generated by this linear fitting were highly consistent with those by the normal nonlinear approach (P > 0.05). The K^trans maps were consistent with the normally derived maps in pattern distribution but the absolute value might be scaled due to the assumption of the reference K^trans value.

Conclusion:

This novel method generates reliable and consistent physiological parameter maps with significantly lower computation complexity than the multiparameter nonlinear fitting. The DCE‐MRI scan time can be greatly shortened without T₁ mapping. J. Magn. Reson. Imaging 2012;35:916–925. © 2011 Wiley Periodicals, Inc.     

Vessel size imaging using dual contrast agent injections

Purpose:

To investigate the feasibility of a vessel size imaging (VSI) technique with separate contrast agent injections for evaluation of the vessel caliber in normal tissues and in brain tumors.

Materials and Methods:

Computer simulation was first performed to assess the potential errors in the estimation of vessel caliber that could result from time shifts between the dual contrast agent injections. Eight patients (four female, four male, 37–77 years old) with brain tumors (three high‐grade gliomas, two low‐grade gliomas, and three meningiomas) were recruited for clinical study. Dynamic susceptibility contrast magnetic resonance imaging (MRI) using gradient echo (GE) and spin echo (SE) echo‐planar imaging sequences were performed separately with a 10‐minute interval on a 3.0T scanner. Vessel caliber maps were calculated and analyzed in regions of interest at cortical gray matter (GM), thalamus, white matter (WM), and tumors.

Results:

From the computer simulation, the error of vessel caliber measurement was less than 8% when the difference between the time‐to‐peak of the GE and the SE studies was 1.5 seconds, and reduced to within 5% when the difference was 1 second. From the patient datasets of a 64 × 64 matrix, the estimated vessel calibers were 37.4 ± 12.9 μm for cortical gray matter, 20.7 ± 8.8 μm for thalamus, and 15.0 ± 5.1 μm for white matter, comparable to results in the literature. Two patients had a VSI with 128 × 128 matrix and showed similar results in vessel calibers of normal tissues. All the tumors had larger mean vessel diameter than normal‐appearing tissues. The difference in vascular size between normal tissue and tumor was demonstrated clearly in both the VSIs of regular and high spatial resolution.

Conclusion:

This study suggests that VSI with a dual injection method is a feasible technique for estimating microvascular calibers of normal tissues and brain tumors in clinical scanners. J. Magn. Reson. Imaging 2009;30:1078–1084. © 2009 Wiley‐Liss, Inc.     

Application of a biodegradable macromolecular contrast agent in dynamic contrast‐enhanced MRI for assessing the efficacy of indocyanine green‐enhanced photothermal cancer therapy

Purpose

To investigate the effectiveness of a polydisulfide‐based biodegradable macromolecular contrast agent, (Gd‐DTPA)‐cystamine copolymers (GDCC), in assessing the efficacy of indocyanine green‐enhanced photothermal cancer therapy using dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI).

Materials and Methods

Breast cancer xenografts in mice were injected with indocyanine green and irradiated with a laser. The efficacy was assessed using DCE‐MRI with GDCC of 40 kDa (GDCC‐40) at 4 hours and 7 days after the treatment. The uptake of GDCC‐40 by the tumors was fit to a two‐compartment model to obtain tumor vascular parameters, including fractional plasma volume (f^PV), endothelium transfer coefficient (K^PS), and permeability surface area product (PS).

Results

GDCC‐40 resulted in similar tumor vascular parameters at three doses, with larger standard deviations at lower doses. The values of f^PV, K^PS, and PS of the treated tumors were smaller (P < 0.05) than those of untreated tumors at 4 hours after the treatment and recovered to pretreatment values (P > 0.05) at 7 days after the treatment.

Conclusion

DCE‐MRI with GDCC‐40 is effective for assessing tumor early response to dye‐enhanced photothermal therapy and detecting tumor relapse after the treatment. GDCC‐40 has a potential to noninvasively monitor anticancer therapies with DCE‐MRI. J. Magn. Reson. Imaging 2009;30:401–406. © 2009 Wiley‐Liss, Inc.     

Added value of breathhold diffusion‐weighted MRI in detection of small hepatocellular carcinoma lesions compared with dynamic contrast‐enhanced MRI alone using receiver operating characteristic curve analysis

Purpose

To evaluate the added value of single‐breathhold diffusion‐weighted MRI (DWI) in detection of small hepatocellular carcinoma (HCC) lesions (≤2 cm) in patients with chronic liver disease, by comparing the detection sensitivity of combined DWI/conventional dynamic contrast‐enhanced (DCE)‐MRI to that of conventional DCE‐MRI alone.

Materials and Methods

A total of 37 patients with chronic liver diseases underwent abdominal MRI at 1.5T, including T1‐weighted imaging (T1WI), T2‐weighted imaging (T2WI), and 2D conventional DCE. For each patient study, axial DWI was performed with a single‐shot echo‐planar imaging (EPI) sequence using a modified sensitivity‐encoding (mSENSE) technique with b‐value of 500 seconds/mm². A total of 20–24 slices were obtained during a 15–17‐second breathhold. Two observers independently interpreted the combined DWI/conventional DCE‐MRI images and the conventional DCE‐MRI images alone in random order. For all small HCC lesions, the diagnostic performance using each imaging set was evaluated by receiver operating characteristic (ROC) curve analysis. Sensitivity and positive predictive values were also calculated and analyzed.

Results

A total of 47 small HCCs were confirmed as final result. The area under the ROC curve (Az) of combined DWI/conventional DCE‐MRI images (observer 1, 0.922; observer 2, 0.918) were statistically higher than those of conventional DCE‐MRI alone (observer 1, 0.809; observer 2, 0.778) for all small HCC lesions (P < 0.01). The lesion detection sensitivities using the combined technique for both observers were significantly higher than those using conventional DCE‐MRI alone (P < 0.01). The sensitivity values for two observers using the combined technique were 97.87% and those using conventional DCE‐MRI alone were 85.11% to 82.98%. The positive predictive values for two observers using the combined imaging technique (97.87%) were slightly higher than those using conventional DCE‐MRI alone (92.86–93.02%), but there was no significant difference between the two imaging sets.

Conclusion

Combined use of breathhold DWI with conventional DCE‐MRI helped to provide higher sensitivities than conventional DCE‐MRI alone in the detection of small HCC lesions in patients with chronic liver disease. J. Magn. Reson. Imaging 2009;29:341–349. © 2009 Wiley‐Liss, Inc.     

Dynamic contrast-enhanced magnetic resonance imaging and invasive breast cancer: primary lesion kinetics correlated with axillary lymph node extracapsular extension

Purpose

To determine if dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) peak enhancement (PE) of primary breast cancer can predict the presence of lymph node extracapsular extension (LNECE) in patients with axillary metastatic disease.

Materials and Methods

In all, 167 patients treated with radiotherapy for invasive breast cancer from January 1, 2006 to November 1, 2007 were retrospectively identified. Patients with DCE‐MRI and surgical axillary staging were included in this study. PE of primary tumors was compared according to axillary nodal status: negative, positive without LNECE, or positive with LNECE. A receiver operator characteristic curve (ROC) was plotted to determine accuracy of PE to predict LNECE.

Results

Forty‐six patients met the study criteria. Thirty‐two (70%) were node‐negative, 9 (19%) were node‐positive without LNECE, and 5 (11%) were node‐positive with LNECE. PE was greater for patients with LNECE (mean 365%) compared to node‐positive patients without LNECE (mean 183%) P = 0.05 and node‐negative patients (mean 144%) P = 0.0012. Area under the ROC curve was 0.93.

Conclusion

DCE‐MRI PE may be a surrogate marker for LNECE. If validated, DCE‐MRI may provide noninvasive kinetic information informing axillary nodal status for patients who receive chemotherapy prior to surgical axillary staging or forego axillary dissection after a positive sentinel node biopsy. J. Magn. Reson. Imaging 2011;33:96–101. © 2010 Wiley‐Liss, Inc.     

Washout gradient in dynamic contrast-enhanced MRI is associated with tumor aggressiveness of prostate cancer

Purpose:

To investigate the associations between dynamic contrast‐enhanced magnetic resonance imaging (DCE MRI) parameters and the Gleason score (GS) for prostate cancer (PCA) with localization information provided by concurrent apparent diffusion coefficient (ADC) maps.

Materials and Methods:

Forty‐three male patients received MR scans, including diffusion tensor imaging (DTI) and DCE MRI, on a 1.5 T MR system. All patients were confirmed to have PCA in the following biopsy within 2 weeks. ADC maps calculated from DTI were used to colocalize cancerous and noncancerous regions on DCE MRI for perfusion analysis retrospectively. Semiquantitative parameters (peak enhancement, initial gradient, and washout gradient [WG] and quantitative parameters [K^trans, ν_e, and k_ep]) were calculated and correlated with the GS. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of the perfusion parameters in assessing the aggressiveness of PCA.

Results:

A total of 41 PCA nodules were included in the analysis. Among all quantitative and semiquantitative parameters, only WG showed significant correlation with GS (r = ?0.75, P < 0.0001). By defining tumor aggressiveness as a GS >6, WG demonstrated a good diagnostic performance, with the area under the ROC curve being 0.88. Under a cutoff point of WG = 0.125 min^?1, the sensitivity and specificity were 0.87 and 0.78, respectively.

Conclusion:

WG shows a significant association with GS and good diagnostic performance in assessing tumor aggressiveness. Therefore, WG is a potential marker of GS. J. Magn. Reson. Imaging 2012;36:912–919. © 2012 Wiley Periodicals, Inc.

     

A dedicated automated injection system for dynamic contrast‐enhanced MRI experiments in mice

Purpose:

To develop a reproducible small‐animal dynamic contrast‐enhanced (DCE) MRI set‐up for mice through which volumes <100 μL can be accurately and safely injected and to test this set‐up by means of DCE measurements in resting muscle and tumor tissue.

Materials and Methods:

The contrast agent (CA) injection system comprised 2 MR‐compatible syringe pumps placed 50 cm from the 7T magnet bore where the fringe field is approximately 40 mT. Microbore tubing and T‐connector, close to the injection site, minimized dead volume (<10 μL). For DCE‐MRI measurements in 8 CB‐17 SCID mice with 1500–2500 mm³ large orthotopic neuroblastoma, a bolus of 10‐fold‐diluted Gd‐DTPA CA solution (0.1 mmol/kg) was delivered (5 μL/s), followed by a 50‐μL saline flush. Retro‐orbital injections were given instead of tail vein injections, because the peripheral vasculature was reduced because of large tumor burden.

Results:

The CA injection was successful in 19 of 24 experiments. Optical assessment showed minimal dispersion of ink‐colored CA bolus. Mean (±SD) pharmacokinetic parameters retrieved from DCE‐MRI examinations in resting muscle (K^trans = 0.038 ± 0.025 min^?1, k_ep = 0.66 ± 0.48 min^?1, v_e = 0.060 ± 0.014, v_p = 0.033 ± 0.021) and tumor (K^trans = 0.082 ± 0.071 min^?1, k_ep = 0.82 ± 0.80 min^?1, v_e = 0.121 ± 0.075, v_p = 0.093 ± 0.051) agreed with those reported previously.

Conclusion:

We successfully designed and implemented a DCE‐MRI set‐up system with short injection lines and low dead volume. The system can be used at any field strength with the syringe pumps placed at a sufficiently low fringe field (<40 mT). J. Magn. Reson. Imaging 2013;37:746–751. © 2012 Wiley Periodicals, Inc.

     

Relationship of temporal resolution to diagnostic performance for dynamic contrast enhanced MRI of the breast

Purpose:

To investigate the relationship between temporal resolution of dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) and classification of breast lesions as benign versus malignant.

Materials and Methods:

Patients underwent T₁‐weighted DCE MRI with 15 s/acquisition temporal resolution using 1.5 Tesla (n = 48) and 3.0T (n = 33) MRI scanners. Seventy‐nine patients had pathologically proven diagnosis and 2 had 2 years follow‐up showing no change in lesion size. The temporal resolution of DCE MRI was systematically reduced as a postprocessing step from 15 to 30, 45, and 60 s/acquisition by eliminating intermediate time points. Average wash‐in and wash‐out slopes, wash‐out percentage changes, and kinetic curve shape (persistently enhancing, plateau, or wash‐out) were compared for each temporal resolution. Logistic regression and receiver operating characteristic (ROC) curve analysis were used to compare kinetic parameters and diagnostic accuracy.

Results:

Sixty patients (74%) had malignant lesions and 21 patients (26%) had benign lesions. All temporal‐resolution parameters significantly predicted benign versus malignant diagnosis (P < 0.05). However, 45 s/acquisition and higher temporal‐resolution datasets showed higher accuracy than the 60 s/acquisition dataset by ROC curve analysis (0.72 versus 0.69 for average wash‐in slope; 0.85 versus 0.82, for average wash‐out slope; and 0.88 versus 0.80 for kinetic curve shape assessment, for 45 s/acquisition versus 60 s/acquisition temporal‐resolution datasets, respectively (P = 0.027).

Conclusion:

DCE MRI data with at least 45‐s temporal resolution maximized the agreement between the kinetic parameters and correct classification of benign versus malignant diagnosis. J. Magn. Reson. Imaging 2009;30:999–1004. © 2009 Wiley‐Liss, Inc.     

Correlations between dynamic contrast-enhanced magnetic resonance imaging-derived measures of tumor microvasculature and interstitial fluid pressure in patients with cervical cancer

Purpose

To correlate permeability (rk_trans), extracellular volume fraction (rv_e), relative to muscle and initial area under the enhancement curve (IAUC_60m) determined by dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) with in vivo measurements of interstitial fluid pressure (IFP) in patients with cervical cancer.

Materials and Methods

DCE‐MRI and IFP measurements were performed of cervical tumors of 32 patients prior to therapy. Median tumor rk_trans and rv_e were derived from a bidirectional two‐compartment model using an input function derived from muscle. Median IAUC_60m was defined as the integral of tumor enhancement in the first 60 seconds divided by the similar muscle enhancement integral. These parameters were correlated with the mean tumor IFP.

Results

There was a significant negative correlation between IAUC_60m and IFP (r = –0.42, P = 0.016) and between rk_trans and IFP (r = –0.47, P = 0.008). The was no significant correlation between IFP and rv_e.

Conclusion

There is a moderate negative correlation between IAUC_60m, rk_trans, and IFP in cervical cancer. This suggests that these parameters may be of value in assessment of tumor behavior. J. Magn. Reson. Imaging 2007. © 2006 Wiley‐Liss, Inc.     

Limitations of dynamic contrast-enhanced MRI in monitoring radiation-induced changes in the fraction of radiobiologically hypoxic cells in human melanoma xenografts

Purpose

To investigate the potential of gadopentetate dimeglumine (Gd‐DTPA)‐based dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) in detecting radiation‐induced changes in the fraction of radiobiologically hypoxic cells in A‐07 human melanoma xenografts.

Materials and Methods

A‐07 tumors were randomly assigned to an unirradiated control group or a group given a single radiation dose of 20 Gy. DCE‐MRI and measurement of fraction of hypoxic cells were performed immediately before and 24 h after the radiation exposure. Tumor images of E · F (E is the initial extraction fraction of Gd‐DTPA and F is blood perfusion) and λ (λ is proportional to extracellular volume fraction) were produced by subjecting DCE‐MRI series to Kety analysis. Fraction of hypoxic cells was measured by using a radiobiological assay based on the paired survival curve method.

Results

Fraction of radiobiologically hypoxic cells was higher in irradiated tumors (26.2 ± 5.8%) than in unirradiated tumors (7.5 ± 2.7%) by a factor of 3.5 ± 1.5 (P = 0.0093), whereas only minor radiation‐induced changes in E · F and λ could be detected.

Conclusion

DCE‐MRI does not seem to offer insight into the changes in fraction of radiobiologically hypoxic cells occurring in A‐07 tumors within 24 h after irradiation with 20 Gy. J. Magn. Reson. Imaging 2008;28:1209–1218. © 2008 Wiley‐Liss, Inc.     

Pharmacokinetic mapping for lesion classification in dynamic breast MRI

Purpose:

To prospectively investigate whether a rapid dynamic MRI protocol, in conjunction with pharmacokinetic modeling, could provide diagnostically useful information for discriminating biopsy‐proven benign lesions from malignancies.

Materials and Methods:

Patients referred to breast biopsy based on suspicious screening findings were eligible. After anatomic imaging, patients were scanned using a dynamic protocol with complete bilateral breast coverage. Maps of pharmacokinetic parameters representing transfer constant (K^trans), efflux rate constant (k_ep), blood plasma volume fraction (v_p), and extracellular extravascular volume fraction (v_e) were averaged over lesions and used, with biopsy results, to generate receiver operating characteristic curves for linear classifiers using one, two, or three parameters.

Results:

Biopsy and imaging results were obtained from 93 lesions in 74 of 78 study patients. Classification based on K^trans and k_ep gave the greatest accuracy, with an area under the receiver operating characteristic curve of 0.915, sensitivity of 91%, and specificity of 85%, compared with values of 88% and 68%, respectively, obtained in a recent study of clinical breast MRI in a similar patient population.

Conclusion:

Pharmacokinetic classification of breast lesions is practical on modern MRI hardware and provides significant accuracy for identification of malignancies. Sensitivity of a two‐parameter linear classifier is comparable to that reported in a recent multicenter study of clinical breast MRI, while specificity is significantly higher. J. Magn. Reson. Imaging 2010;31:1371–1378. © 2010 Wiley‐Liss, Inc.     

Dynamic contrast-enhanced MRI of primary rectal cancer: quantitative correlation with positron emission tomography/computed tomography

Purpose

To assess the correlations between parameters measured on dynamic contrast‐enhanced magnetic resonance imaging and 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) in rectal cancer.

Materials and Methods

To assess the correlations between parameters measured on dynamic contrast‐enhanced MRI and FDG‐PET in rectal cancer.

Results

Significant correlations were only demonstrated between k_ep and SUVmax (r = 0.587, P = 0.001), and k_ep and SUVmean (r = 0.562, P = 0.002). No significant differences were found in imaging parameters between well, moderately and poorly differentiated adenocarcinoma groups. However, there was a trend that higher imaging values were found in poorly differentiated adenocarcinomas.

Conclusion

Positive correlations were found between k_ep and SUV values in primary rectal adenocarcinomas suggesting an association between angiogenesis and metabolic activity and further reflecting that angiogenic activity in washout phase is better associated with tumor metabolism than the uptake phase. J. Magn. Reson. Imaging 2011;33:340–347. © 2011 Wiley‐Liss, Inc.     

Sampling requirements in DCE‐MRI based analysis of high grade gliomas: Simulations and clinical results

Purpose:

To investigate the effect of variations in temporal resolution and total measurement times on the estimations of kinetic parameters derived from dynamic contrast‐enhanced (DCE) MRI in patients with high‐grade gliomas (HGGs).

Materials and Methods:

DCE‐MRI with high temporal resolution (dynamic sampling time (T_s) = 2.1 s and 3.4 s) and total sampling time (T_acq) of 5.2 min was acquired in 101 examinations from 15 patients. Using the modified Tofts model K^trans, k_ep v_e and v_p were estimated. The effects of increasing T_s and reducing T_acq on the estimated kinetic parameters were estimated through down‐sampling and data truncation, and the results were compared with numerical simulations.

Results:

There was an overall dependence of all four kinetic parameters on T_s and T_acq. Increasing T_s resulted in under‐estimation of K^trans and over‐estimation of V_p, whereas k_ep and V_e varied in a less predictable manner. Reducing T_acq resulted in over‐estimation of K^trans and k_ep and under‐estimation of v_p and v_e. Increasing T_s and reducing T_acq resulted in increased relative error for all four parameters.

Conclusion:

Estimated K^trans, K_ep, and V_e in HGGs were within 15% of the high sampling rate reference values for T_s<20 s. Increasing T_s and reducing T_acq leads to reduced precision of the estimated values. J. Magn. Reson. Imaging 2013;37:818–829. © 2012 Wiley Periodicals, Inc.     

Dynamic Contrast-Enhanced MRI for Monitoring Antiangiogenic Treatment: Determination of Accurate and Reliable Perfusion Parameters in a Longitudinal Study of a Mouse Xenograft Model

Objective

To determine the reliable perfusion parameters in dynamic contrast-enhanced MRI (DCE-MRI) for the monitoring antiangiogenic treatment in mice.

Materials and Methods

Mice, with U-118 MG tumor, were treated with either saline (n = 3) or antiangiogenic agent (sunitinib, n = 8). Before (day 0) and after (days 2, 8, 15, 25) treatment, DCE examinations using correlations of perfusion parameters (K_ep, K_el, and A^H from two compartment model; time to peak, initial slope and % enhancement from time-intensity curve analysis) were evaluated.

Results

Tumor growth rate was found to be 129% ± 28 in control group, -33% ± 11 in four mice with sunitinib-treatment (tumor regression) and 47% ± 15 in four with sunitinib-treatment (growth retardation). K_ep (r = 0.80) and initial slope (r = 0.84) showed strong positive correlation to the initial tumor volume (p < 0.05). In control mice, tumor regression group and growth retardation group animals, K_ep (r : 0.75, 0.78, 0.81, 0.69) and initial slope (r : 0.79, 0.65, 0.67, 0.84) showed significant correlation with tumor volume (p < 0.01). In four mice with tumor re-growth, K_ep and initial slope increased 20% or greater at earlier (n = 2) than or same periods (n = 2) to when the tumor started to re-grow with 20% or greater growth rate.

Conclusion

K_ep and initial slope may a reliable parameters for monitoring the response of antiangiogenic treatment.     

In vivo imaging of vessel diameter,size, and density: A comparative study between MRI and histology

The aim of this study was to compare magnetic resonance imaging (MRI) and histological estimates of the mean vessel diameter (mVD), the vessel density (Density), and the vessel size index (VSI) obtained in the same tumor‐bearing animals. Twenty‐seven rats bearing intracranial glioma (C6 or RG2) were imaged by MRI. Changes in transverse relaxations (ΔR and R₂) were induced by the injection of an iron‐based contrast agent and were mapped using a multi gradient‐echo spin‐echo sequence. Then, brain vascular network was studied ex vivo by histology. Three regions of interest were drawn in apparently normal tissue (neocortex and striatum) and in the tumor. In vivo mVD_MRI, Density_MRI, and VSI_MRI were measured; ex vivo, mVD_histo, Density_histo, and VSI_histo were quantified on the same animals. MRI and histology measurements differed by ?15 to 26%. A positive correlation was found between MRI and histology for mVD, Density, and VSI counterparts (R² = 0.62, 0.50, 0.73, respectively; P < 0.001 in all cases). This study indicates that MRI and histology yields well correlated the estimates of mVD, Density, and VSI. VSI is the closest MRI estimate to histology. As Density and mVD or VSI provide complementary information, it is worth computing them to characterize angiogenesis beyond blood volume fraction. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.