Conventional Fourier Sampling Ultrafast Methods

Jansen et al, ³⁵ Pinker et al, ⁵⁴ and Planey et al ⁵⁶ used the conventional Fourier sampling methods to image contrast media uptake in the breast at high temporal resolution. Improvements in temporal resolution in these studies came at the expense of either greatly reduced coverage, or lower spatial resolution than standard clinical scans (e.g., Pinker et al reduced spatial resolution from 1 mm to 1.7 mm isotropic voxels). ⁵⁴ Nevertheless, these studies showed advantages in conspicuity of pre-invasive lesions, and estimation of pharmacokinetic parameters compared to standard, low temporal resolution, clinical scans.

Studies at the University of Chicago characterized the kinetics of early enhancement in arteries, veins, malignant lesions, benign lesions, and normal-appearing parenchyma; and evaluated the performance of parameters descriptive of early kinetics in differentiating malignant versus benign lesions. Potential advantages in lesion detectability were also investigated. The protocol used the conventional Fourier sampling to allow robust quantitative analysis and a novel filtering and analysis method to identify rapidly enhancing lesions. The acquisition protocol used in these studies can be easily implemented in a clinical setting, regardless of vendor or scanner type. Images were acquired at lower spatial resolution and relatively high SENSE (parallel imaging) acceleration factors during the first minute postcontrast injection, to produce full bilateral, fat-suppressed breast images with temporal resolution ranging between 6.2 and 9.9 seconds (higher temporal resolutions are possible with this protocol, particularly at 3 T). Following an initial 60 seconds of fast imaging, subsequent images were acquired using a standard clinical protocol with high spatial resolution, intermediate SENSE factors, and low temporal resolution. Table 3‑1 compares acquisition parameters for the conventional DCE-MRI and the ultrafast imaging.

The ultrafast images during the first minute after contrast media injection provide detailed information regarding the early kinetics in the breast, while later high spatial resolution acquisitions allow assessment of the morphology of small lesions. The results provide new information regarding contrast media uptake kinetics during the first minute after injection and demonstrate the potential diagnostic utility of high temporal resolution imaging.

In an initial pilot study, ^{31 ,​ 32} ultrafast DCE-MRI was performed on 23 patients with biopsy proven lesions or lesions detected on prior imaging, including a mix of ductal carcinoma in situ (DCIS), invasive cancers, and benign lesions. The study was performed on a Philips Achieva 3T-TX scanner using a 16-channel bilateral breast coil. The DCE series consisted of one standard clinical acquisition, ultrafast acquisitions for 50 to 80 seconds after injection, followed by four standard clinical acquisitions (with the protocols described in Table 3‑1). Contrast media (0.1 mM/kg gadobenate dimeglumine; MultiHance, Bracco, NJ) was injected IV at 2 mL/s.

Arterial enhancement was easily visualized in maximum intensity projections (MIPs), identifying the time at which the contrast media reaches the breast. Thus, lesion enhancement was measured relative to the time of arrival of the contrast bolus in the mammary arteries, rather than the time of injection. This removed variability due to systemic physiology, for example, cardiac output. A digital filter was developed to identify significantly enhancing voxels, and to reduce spurious enhancement due to noise or artifacts. Only pixels with significant and stable enhancement were used for kinetic analysis.

Regions of interest (ROIs) were drawn around the lesions on ultrafast and standard clinical images (at each time point), under radiologists’ guidance, and average signal enhancement was measured at each time point. Background parenchymal enhancement (BPE) was measured for all cases by manually segmenting the parenchyma in a slice in the central part of the breast without any lesions present and measuring the average signal intensity at each time-point. The signal intensity in the blood vessels feeding the lesions was also measured for each time point. Percent signal enhancement (PSE) versus time data were fit to a truncated (uptake only) empirical mathematical model (EMM) for malignant lesions, benign lesions, and parenchyma, ^{57 ,​ 58} for only the high temporal resolution time-points ^{57 ,​ 58 ,​ 59}

Where A is the upper limit of percent enhancement, and α is the uptake rate (sec^-1). From the EMM parameters, three secondary parameters were calculated: (1) initial area under the contrast enhancement versus time curve (iAUC), ⁶⁰ (2) time to 90% of maximum enhancement (T90), and (3) initial slope (defined as the product of the uptake rate and the upper limit of enhancement). T90 was used as a surrogate for time-to-peak enhancement.

Lesion conspicuity was quantified by calculating the ratio of signal increase in the lesion to the signal increase of normal parenchyma at each time-point:

MIPs from ultrafast DCE-MRI (Fig. 3‑3 a-d) standard subtractions, (Fig. 3‑3g,h) enhancement gradient, show signal increase in the vessels, including very early enhancement in tortuous vessels directly feeding tumors followed by signal increase in the tumors. The enhancement gradient images (each image subtracted from the immediately succeeding image) show a slowing signal increase in the arteries, and in Fig. 3‑3g a blood vessel posterior and lateral to the lesions is seen enhancing immediately after enhancement of the lesion; this is likely a vein draining the tumor. For most cases (19 out of 20), significant arterial enhancement (> 20%) was measured in the second or third ultrafast postcontrast image, in the internal mammary artery. For three cases, the vessel feeding the lesion began to enhance at the same time as the internal mammary artery. In all other cases, the vessel feeding the lesion enhanced later than the internal mammary artery.

The average percentage of significantly enhancing voxels in the whole field-of-view (FOV) started at 0.4% of the FOV at the first time-point post injection (when in most cases only the heart was enhanced) and monotonically rose to 5.7 ± 1.9% at the fourth time point, and 7.3 ± 2.5% of the entire FOV by the last ultrafast acquisition. This means that enhancement at early times after contrast injection is very sparse.

Time-to-enhancement (TTE) maps were created as a way of visualizing the time at which lesions began enhancing and the heterogeneity of the TTE within lesions. Examples of these maps can be seen in (Fig. 3‑4), for both malignant and benign lesions. The results shown are typical of the lesions imaged; the average TTE was much shorter (p < 0.01) for malignant lesions (18.4 ± 12.9 seconds) than for benign lesions (43.5 ± 36.1 seconds). Intralesion heterogeneity in TTE can also be appreciated in these maps. In benign ROIs, the average intralesion coefficient of variation in TTE was 0.58 ± 0.37, and in malignant lesions was 0.38 ± 0.51. Thus, heterogeneous enhancement patterns at early times after injection may be an additional marker for cancers that is only available from ultrafast DCE-MRI.

Average signal enhancement from the ROIs, as a function of time relative to the time of injection, is plotted in (Fig. 3‑5) for malignancies (n = 18), benign findings (n = 15), and BPE (n = 20). On average malignancies enhanced strongly throughout the first minute relative to benign lesions and parenchyma. The average EMM fits to the data from malignant lesions, benign lesions, and parenchyma are also plotted as solid lines, using the average value of arterial time-of-arrival, 11.6 ± 5.8 seconds relative to the injection time, for illustration purposes. Significant differences (post-Bonferroni corrections) were found between benign and malignant lesions for EMM parameters related to the rate of early enhancement.

Lesion conspicuity (across all lesions) was highest during the early ultrafast acquisitions, particularly at the fourth ultrafast acquisition postinjection, where its average was 11:1. The difference between ultrafast and conventional acquisitions was most pronounced in cases with marked BPE. For all these cases, the maximum conspicuity of the lesions occurs too early to be detectable in the standard clinical protocol. Subtraction images for three-time points sampled with ultrafast imaging and the first time-point of the standard clinical protocol, from two of the cases (a fibroadenoma and a satellite invasive ductal carcinoma [IDC]) can be seen in (Fig. 3‑6 ).

These preliminary results show that ultrafast imaging accurately measures the early kinetics of enhancement in lesions, blood vessels, and parenchyma. Ultrafast imaging allowed analysis of the TTE data with respect to the time of initial arterial enhancement. In addition the speed of propagation of the arterial bolus can be measured – and used to estimate arterial blood flow. This is not possible in conventional DCE-MRI with temporal resolution more than 1 minute. As a result, ultrafast imaging allows evaluation of the local vasculature characteristics while reducing the influence of global variables such as cardiac output. The results suggest that ultrafast imaging may detect early enhancement of lesions that occurs before parenchymal enhancement, thus making lesions more conspicuous; this is especially useful in cases with marked parenchymal enhancement (i.e., younger women). ^{61 ,​ 62 ,​ 63} This is consistent with earlier results obtained by scanning a limited number of slices (include suspicious lesions and their surroundings) with 7-second temporal resolution and demonstrating that this approach detects significant differences between the early enhancement of DCIS and normal parenchyma, thus improving conspicuity of small diffuse cancers. The differences in average values of some of the kinetic parameters between benign and malignant lesions were very large, suggesting a large dynamic range for ultrafast parameters.

Although the current protocol used clinically at the University of Chicago allows detection of approximate “initial time of enhancement” in arteries and veins, the temporal resolution is not adequate to resolve the detailed shape of the contrast media bolus. Higher temporal resolution would allow accurate measurement of the AIF and precise arrival time of the bolus. These parameters can be combined with standard measures of contrast media uptake to increase diagnostic accuracy.

This study was performed on a 3 T scanner, while the majority of clinical scans in the United States are performed at 1.5 T. ¹¹ A similar protocol has been implemented on a 1.5 T scanner with somewhat lower temporal resolution (at least 9 seconds) and good image quality. The protocol described here is used as the clinical protocol at the University of Chicago (at both 1.5 T and 3 T).

Mori et al implemented a similar ultrafast protocol at 1.5 T with a temporal resolution of 10 seconds (Table 3‑2). Image quality and enhancement kinetics of lesions were evaluated in a study of 33 patients imaged with this protocol, with 33 lesions present (15 benign and 18 malignant). SNR was calculated for each case using the method described by Yu et al. ⁶⁴ The SNR of the ultrafast DCE-MRI was found to be lower than that of the standard DCE-MRI acquisition, however the difference was not statistically significant (Fig. 3‑7a). Lesion contrast-to-noise ratio was calculated by comparing the signals in the fibroglandular tissue and the lesions of interest (as described by Song et al). ⁶⁵ The CNR in the phase when enhancement in the aorta was first detected, and in the time point immediately following it were lower than in the rest of the ultrafast phases and in the initial standard DCE phase (Fig. 3‑7b). Lesion conspicuity with respect to BPE was also calculated; lesion conspicuity (or contrast ratio) was higher in the ultrafast images than in the early standard images. However, these differences were not significant (Fig. 3‑7c). The difference in the lesion conspicuity between ultrafast and conventional images was most pronounced in cases with marked BPE.

In another study by Mori et al, ⁶⁶ this one performed on a 3 T scanner (Table 3‑3), the performance of using early lesion enhancement for classification of lesions was assessed. 37 patients with 15 benign and 22 malignant lesions were included in this analysis. Axial maximum projection images using this 3 second ultrafast protocol at 3 T are shown in Fig. 3‑8. Relative enhancement rate was calculated in a voxel-by-voxel basis in each lesion ROI. The percent lesion enhancement in the different ultrafast phases was compared between benign and malignant lesions by analyzing the histograms of relative enhancement for the entire ROI. The values from the 50th percentile of the histograms up to the maximally enhancing voxels were calculated for each lesion. Statistically significant differences were found between the relative enhancement of benign and malignant lesions, especially in the first 2 time points following aortic enhancement. For example, the 90th percentile values of enhancement in the first time-point following aortic enhancement were 111 ± 67%, and 26 ± 29% for malignant and benign lesions, respectively. For the following ultrafast phase, these values were 160 ± 61% and 57 ± 53%, again for malignant and benign lesions, respectively. These two phases were recommended by the authors as the most effective in which to detect the differential leakage of contrast agent between benign and malignant lesions.

Pinker et al reported that a combined high temporal and high spatial resolution protocol (similar to the ones described above) allowed accurate detection and assessment of breast lesions, with a sensitivity of 100% and specificity of 72.2%. ⁵⁴ In this study, ultrafast DCE images were acquired from 34 patients with a temporal resolution of roughly 13 seconds, and contrast media kinetics were sampled for 3.5 minutes after the injection of contrast.

In addition to potentially increased sensitivity, ultrafast imaging may also improve specificity by ruling out cancer in cases where there is no significant lesion enhancement at early times after arrival of the contrast bolus in the breast.