Prostate cancer (PCa) is one of the most common diseases in men. In the US, it accounts for 21% of new cases, and it is the second leading cause of death in men, accounting for 10% of all deaths [1
Multiparameters magnetic resonance imaging (mpMRI) with the assessment of images using the Prostate Imaging Reporting and Data System (PI-RADS) is widely used to evaluate prostate lesions. Dynamic contrast-enhanced (DCE)-MRI is a technique used to measure the perfusion, blood flow, and tissue vascularity by analyzing the tissue’s signal enhancement curve. DCE-MRI, which can assess micro-vascular properties, provides helpful additional information for characterizing lesions [2
]. In many current clinical trials, DCE-MRI for a new anti-angiogenic agent is used as an early imaging biomarker to evaluate patients’ response to treatment [3
]. Microvessel density has been reported to be associated with tumor stage, recurrence, metastatic potential, and prognosis in patients with prostate cancer [4
]. This signal enhancement of perfusion can be quantified with semi-quantitative analysis [7
]. Semi-quantitative parameters can be extracted and calculated from the signal intensity curve [9
]. The signal intensity curve reveals several parameters, including arrival time (AT), time to peak (TTP), wash-in slope (W-in), wash-out slope (W-out), peak enhancement intensity (PEI), and initial area under the 60-sec curve (iAUC). AT is arrival time, which is the time point when contrast enhancement starts. TTP is time to peak, which is the time from arrival time to the end of wash-in. A shorter TTP indicates the shorter time needed to reach the peak. Wash-in slope is the slope of the fitted line between AT and the end of wash-in. The higher W-in is, the faster the wash-in speed. W-out slope is the fitted line slope between the start of wash-out and the end of the measurement. The higher the W-out is, the faster the wash-out speed. PEI indicates the highest value of enhancement. And iAUC calculates the initial area under the curve in 60 s, reflecting the total intensity of enhancement during the first one minute.
Molecular imaging of prostate cancer is a beneficial tool for systematically evaluating tumor biology [11
]. Agents targeting cell metabolism, hormone receptors, or membrane proteins have been developed to an advanced stage. Over the last few years, prostate-specific membrane antigen (PSMA) have gained much interest as specific targets for PCa imaging, which is a promising and specific target. It is a transmembrane glycoprotein related to tumor progression and disease recurrence that has been found to be overexpressed in prostate cancer cells [12
]. PSMA-ligands as prostate cancer-specific PET tracers show and differentiate cancerous lesions within the prostate more accurately than other tracers. A whole-body hybrid PET/MRI scanner with simultaneous acquisition of PET imaging and mpMRI has enabled functional and molecular information to be combined [14
]. Initial results suggest that [68
Ga]Ga-PSMA-11 PET/MRI is a beneficial imaging method for detecting suspicious focal prostate cancer lesions [17
] and monitoring recurrence [19
]. Combining MRI and positron emission tomography (PET) improves diagnostic accuracy [20
]. Compared with the current standard imaging like CT, MRI, and bone scintigraphy, PSMA-PET imaging shows a higher specificity and sensitivity and is suitable for patients with primary middle-risk or high-risk prostate cancer [22
Therefore, this study’s purpose was to retrospectively compare the perfusion parameters of DCE-MRI of prostate benign lesions and malignant lesions, and determine the correlation between these perfusion parameters.
DCE-MRI is an important diagnostic method in detecting focal prostate cancer lesions, which improves the accuracy of examination for detection and evaluation of intraprostatic tumor lesions [23
]. It visualizes focal lesions in the prostate with varying degrees of enhancement and provides information for lesion characterization. Combining the advantages of [68
Ga]Ga-PSMA-11 PET/MRI and DCE-MRI contributes to a better differentiation of intraprostatic lesions [24
]. PSMA-PET imaging can add molecular information to multiparameter MRI to describe suspicious lesions for target biopsy [25
]. The clinical value of this study is the quantitative analysis of the multimodality characteristics of the lesions. DCE parameters reflect lesions’ microvascular structure, while SUVmax reflects lesions’ prostate-specific membrane antigen concentration. A combination of information allows for a comprehensive evaluation of tumor condition and for choosing an appropriate treatment plan.
Intraprostatic lesions perfusion parameters are investigated by several studies before [26
]. Vos et al. [27
] reported that quantitative parameters and semi-quantitative parameters derived from DCE-MRI at 3.0 T MRI could assess the aggressiveness of PCa in the peripheral zone. Chen et al. [28
] proved that the wash-out gradient shows a significant association with Gleason score and good diagnostic performance in assessing prostate tumor aggressiveness. PCa has increased microvascularity and, therefore, can be detected by contrast-enhanced MRI techniques, as van Niekerk et al. reported [29
]. These parameters provide detailed information about the aggressiveness of tumors in different prostate gland regions as, for example, in Figure 1
, Figure 2
and Figure 3
. Therefore, the perfusion differences between prostate benign lesions and malignant lesions may be detected and quantified with DCE-MRI. MpMRI of prostate scanning includes complementary and synergistic T2, diffusion, and perfusion sequences. Ren et al. [30
] proved that DCE-MRI curves could differentiate benign tissue from malignant prostate tissue based on T2-weighted imaging. The omission of DCE-MRI increases the risk that some aggressive lesions will not be detected, thus discrediting prostate imaging by MRI. The sequence of contrast enhancement agents is essential in the detection of recurrence and post-treatment follow-up.
The advantage of the curve analysis method is that it is easy to calculate. Model-based measurement parameters are complex, but they provide more specific information about vascular physiology [31
]. In this study, we compared perfusion parameters between benign lesions and malignant lesions. TTP was significantly different. TTP is the time that contrast enhancement reaches the peak. A shorter TTP indicates the shorter time needed to reach the peak. Then it can be explained that the blood vessels are more abundant in the corresponding lesions. We further divided the lesions into two subgroups. The lesions were divided into two groups in the benign lesion group according to SUVmax ≤ 3.0 and SUVmax > 3.0. All perfusion parameters did not show obvious differences between SUVmax ≤ 3.0 and SUVmax > 3.0. This indicates that SUVmax does not affect the perfusion parameters in benign lesions. In the malignant lesions group, the same results were found.
Moreover, we determined the correlations between perfusion parameters to understand further the physiological significance of semi-quantitative parameters in intraprostatic lesions. They may reflect gross angiogenesis within a focal lesion. AT is arrival time, the point in time when contrast enhancement starts. A shorter AT indicates that the contrast agent flows into the lesion in a shorter time. It further shows that the lesion is rich in blood vessels. W-in is the fitted line’s slope between AT and the end of wash-in, reflecting the speed at which the contrast agent flows into the lesion. The slope is significantly correlated with blood flow so that it can be used to evaluate perfusion within a lesion. Another parameter, iAUC, is the initial area under the curve in 60 s. It suggests that iAUC denotes a combination of blood flow and permeability. These correlations may help select the most suitable semi-quantitative parameter to represent tumor perfusion, flow, and angiogenesis in daily practice.
Angiogenesis is an essential process in tumor growth, and a multitude of pharmacologic therapies primarily target angiogenesis by affecting vascular endothelial growth factor (VEGF) ligand binding [32
]. Microvascular distribution is considered a vital sign of neovascularization, responsible for local growth and tumor metastasis [33
]. In these applications, the potential of PSMA as an imaging biomarker is related to the exact function of PSMA in tumor-related endothelium. Conway et al. [35
] demonstrated that PSMA is required for angiogenesis in vivo and is essential for endothelial cell invasion in vitro. Their results of linking PSMA with p21-activated kinase regulation suggest that PSMA is an important regulator of endothelial cell invasion and angiogenesis and may be a therapeutic target for angiogenesis-related diseases. Chang et al. [36
] proved that PSMA was consistently expressed in the neovasculature of a wide variety of malignant neoplasms. More malignant lesions usually have more abundant microvascular structures [37
]. DCE-MRI is one of the most mature imaging biomarkers of tumor microvessels. DCE-MRI and PSMA-PET can be performed simultaneously in a PET/MRI scanner so that these markers can be directly correlated.
Early research indicated that ADT causes a reduction of blood flow in the prostate gland that precedes apoptosis of the epithelium [41
]. Another study held a different opinion. Roe et al. [43
] reported that their key findings were the increased tumor vascularization following ADT. However, the above experimental conclusions are based on animal experiments. Human studies characterizing vascular effects following ADT are limited. The long-term impact of ADT on tumor vascularization needs to be further investigated. The effects following radiotherapy of prostate measured with quantitative MRI were reported by Kershaw et al. [44
] They proved that tumor blood flow decreased after treatment. Nevertheless, because of this study’s relatively small sample size, a larger number of sample systematic quantitative studies are needed. Therefore, the effect of radiotherapy on the microvascular structure of the human prostate has not been conclusively established. Based on what has been discussed above, ADT and radiotherapy’s effects on microvasculature were not considered in this study. There are some limitations to our study. The patient cohort is relatively small. There are only eleven patients who performed radical prostatectomy (RP) after scanning. Therefore, we were not able to take histopathology results as a gold standard.