SHORT COMMUNICATION

Clinical approach of perfusion- weighted imaging

Perfusion is one of the most important parameters affected on the diagnosis, treatment planning, and disease response to therapy. There are some discriminative kinds of perfusion-weighted imaging (PWI) such as dynamic susceptibility contrast PWI, semiquantitative dynamic contrast-enhanced PWI, quantitative dynamic contrast-enhanced PWI, dynamic glucose-enhanced PWI, arterial spin labelling and amide proton transfer. In this short communication, we aimed to introduce clinical approach of these PWI types. KEYWORDS: perfusion-weighted imaging . magnetic resonance imaging . clinical approach

Introduction per minute per 100 g of brain tissue Nguyen Minh Duc1,2†*, (mL/100g/min). Perfusion, one of the most crucial physiologic Huynh Quang Huy1, Mai and pathophysiologic features of tissue, can be y MTT was equal to CBV/CBF (sec). Tan Lien Bang2, Luc investigated non-invasively and non-ionzingly 3 y TTP was the duration from the 0 second Minh Truong , Pham by magnetic resonance imaging (MRI) [1-5]. 1 to the peak of enhancement (sec). Ngoc Hoa , Pham Minh Currently, we have some different perfusion- Thong4† weighted imaging (PWI) sequences to achieve DSC PWI was predominantly applied in 1Department of Radiology, Pham Ngoc perfusion-related parameters using external assessment of stroke or even brain tumor [1-6]. Thach University of Medicine, Ho Chi tracer such as gadolinium-based contrast agent Minh city, Vietnam (GBCE) or substances and internal tracer such 2Department of Radiology, Childrens „„Semi-quantitative DCE PWI hospital 2, Ho Chi Minh city, Vietnam as blood or water molecule. In practice, we Semiquantitative DCE PWI was simpler 3Department of Radiology, Siemens have two groups of PWI: group A with contrast Healthcare Vietnam, Ho Chi Minh city, than quantitative DCE PWI by utilizing enhancement: (1) dynamic susceptibility contrast Vietnam single multidynamic T1-weighted sequence 4 (DSC) PWI; (2) semiquantitative dynamic Department of Radiology, Hanoi with GBCE. Semi-quantitative DCE PWI medical university, Ha Noi, Vietnam contrast-enhanced (DCE) PWI; (3) quantitative was exploited to achieve parameters relative *Author for correspondence: dynamic contrast-enhanced (DCE) PWI; and enhancement, maximal enhancement, maximal [email protected] (4) dynamic glucose-enhanced (DGE) PWI relative enhancement, T0, time to peak, wash-in and group B without contrast enhancement: rate, wash-out rate, brevity of enhancement and (1) arterial spin labelling (ASL) and (2) amide proton transfer (APT) [1-5]. In this short area under the curve as seen in Figure 2 [7-9]. communication, we aimed to introduce clinical y Relative enhancement was defined as approach of these PWI applications. difference signal intensity of a pixel over all dynamics relative to same pixel in Group A reference dynamic (%). „„DSC PWI y Maximum enhancement was defined DSC PWI might be utilized in estimating as difference maximum signal intensity not only the microvessel area (MVA) but also of a pixel over all dynamics and signal 4 important parameters of lesion included intensity of same pixel in reference cerebral blood volume (CBV), cerebral blood dynamic. flow (CBF), mean time transit (MTT) and time y Relative maximum enhancement was to peak (TTP) derived from multidynamic T2*- defined as maximum signal intensity of weighted gradient recalled echo sequence as seen a pixel over all dynamics relative to same in figure 1 [1-6]. pixel in reference dynamic, 0% indicates y CBV was defined as milliliters of blood the same signal intensity as that in the per 100 g of brain tissue (mL/100g/ reference dynamic (%). min). y T0 was defined as the baseline duration y CBF was defined as milliliters of blood of curve (sec).

ISSN 1755-5191 Imaging Med. (2018) 10(3) 69 SHORT COMMUNICATION Duc, Huy, Bang, et al.

Figure 1. Axial DSC PWI image shows infarction in the left occipital lobe (white arrow) with the reduction of CBV and CBF but the augmentation of MTT and TTP in comparison with the reference.

Figure 2. Axial semi quantitative PWI image shows glioblastoma multiform in the left parietal lobe (white arrow) with the significantly stronger perfusion parameters in comparison with the reference.

70 Imaging Med. (2018) 10(3) Clinical approach of perfusion-weighted imaging SHORT COMMUNICATION

y Time to peak was the duration from the „„Quantitative DCE PWI 0 second to peak of enhancement (sec). Quantitative DCE PWI involves the y Wash-in rate was defined as maximum calculation of perfusion parameters from a time- slope between the time at which the signal intensity curve on the basis of T1 mapping signal intensity increases at least 20% of pre- and post-contrast images. Quantitative compared with the reference dynamic DCE PWI was launched to obtain 4 parameters: and the time of peak enhancement Ktrans, Kep, Ve, and Vp as seen in Figure 6. (sec-1). y Ktrans was defined as volume transfer -3 y Wash-out rate was defined as maximum constant (10 /min). y of absolute value of slope between time Kep was defined as reverse reflux rate of peak and the end of dynamic (sec-1). constant (10-3/min). y y Brevity of enhancement was defined as Ve was defined as volume fraction of -3 the stability of the time signal intensity extravascular extracellular space (10 ). curve. y Vp was defined as volume fraction of -3 y Area under the curve was defined as the plasma (10 ). area under tissue concentration time Quantitative DCE PWI was principally used in curve ultil a stipulated time point that assessment of tumor’s permeability such as breast includes a major portion of the tissue’s tumor (FIGURE 7), prostate tumor (FIGURE response. 8) and brain tumor (FIGURE 9) [1-5]. Semi-quantitative DCE PWI was „„DGE PWI predominantly applied in perfusion assessment DGE PWI was utilized to investigate the of breast tumor (FIGURE 3), liver tumor brain tumor’s consumption of unlabelled (FIGURE 4), bone tumor (FIGURE 5), prostate deoxyglucose (D-glucose). Recently, there tumor and brain tumor [1-9]. are some studies on 7-Tesla MRI revealed the

Figure 3. Axial semi quantitative PWI image shows invasive ductal carcinoma in the left breast (white arrow) with the significantly stronger perfusion parameters in comparison with the reference.

Imaging Med. (2018) 10(3) 71 SHORT COMMUNICATION Duc, Huy, Bang, et al.

Figure 4. Axial semi quantitative PWI image shows the small hepatocellular carcinoma (white arrow) with the significantly strong perfusion and wash-out curve in comparison with the reference.

Figure 5. Axial semi quantitative PWI image shows the malignant fracture (white arrow) with the significantly stronger perfusion parameters in comparison with the reference.

potential of this technique in assessment of brain Group B tumor especially glioblastoma multiform as seen „„ASL in FIGURE 10 [10,11]. In contrast to GBCE, ASL is a perfusion method which does not which is limited in the vascular and extracellular necessitate GBCE as seen in FIGURE 11. ASL extravascular spaces, D-glucose is further utilizes the label arterial blood water proton transported into the intracellular space. Hence, capability as internal contrast-enhanced tracer. DGE PWI produces more information on not CBF was the important parameter arisen from this solely tumor perfusion but also intracellular sequence [12,13]. There are some different kinds glucose consumption [10,11].

72 Imaging Med. (2018) 10(3) Clinical approach of perfusion-weighted imaging SHORT COMMUNICATION

Figure 6. Axial quantitative PWI with gadoxetic acid image shows the hepatocellular adenoma (white arrow) with the same permeability as the reference.

Figure 7. Axial quantitative PWI image shows the small ductal carcinoma in the right breast (white arrow) with the significantly stronger permeability in comparison with the reference.

Imaging Med. (2018) 10(3) 73 SHORT COMMUNICATION Duc, Huy, Bang, et al.

Figure 8. Axial quantitative PWI image shows the prostate carcinoma in the right peripheral zone (white arrow) with the significantly strong permeability.

Figure 9. Axial quantitative PWI image shows the glioblastoma multiform in the left parietal lobe (white arrow) with the significantly strong permeability.

74 Imaging Med. (2018) 10(3) Clinical approach of perfusion-weighted imaging SHORT COMMUNICATION

Figure 10. Accelerated and quantitative T1ρ-weighted dynamic glucose enhanced MRI applied in the study of a patient with a glioblastoma at B0=7T. (A) T2-weighted image acquired at 7T, (B) gadolinium- enhanced T1-weighted (GdCE-T1w) image acquired at 3T, (C) fusion of the GdCE-T1w image and the T1ρ- weighted dynamic glucose enhancement (DGEρ) obtained at t=588 s. (D) Unsmoothed DGEρ time curves with a temporal resolution of less than 7 sec in a tumor-ROI selected on DGEρ (ROI#1), a second tumor-ROI selected on the GdCE-T1w image (ROI#2), and a ROI in normal appearing white matter (ROI #3). The error is given by the standard deviation of 5 consecutive data points and the ROIs are marked in the GdCE-T1w and DGEρ image shown in the top left corner. Increasing DGEρ values are obtained in both tumor-ROIs after the end of the glucose injection. The red arrow marks an abrupt signal drop induced by patient motion. (e–i) DGEρ images (average of 5 consecutive images) at different time points after glucose injection. Note: the hyperintense region at the bottom of the tumor area (black arrow; (G)), which is not visible in the GdCE-T1w image (B). Figure courtesy of Schuenke et al. [10]. of ASL rested on the magnetic labelling procedure: with a synchronous gradient field to mimic a flow-driven adiabatic inversion y Pulsed ASL (PASL) utilizes short (5–20 ms) radio-frequency (RF) pulses to invert seen in CASL without the special a thick slab of spins in the tagging plane hardware [17]. proximal to the imaging region [14]. y Velocity-Selective ASL (VSASL) y Continuous ASL (CASL) uses long and saturates the blood that is moving at a continuous RF pulses (1-2 sec) along faster velocity than the specified cut-off with a constant gradient field to induce value to achieve perfusion contrast [18]. a flow-driven adiabatic inversion in a The main idea in ASL is to obtain a labelled narrow plane of spins, usually just below image and a control image, in which the static the imaging plane [15,16]. tissue signals are identical but the magnetisation y Pseudocontinuous ASL (PCASL) uses a of the inflowing blood is dissimilar. The water train of discrete RF pulses in conjunction molecules in the arterial blood are magnetically

Imaging Med. (2018) 10(3) 75 SHORT COMMUNICATION Duc, Huy, Bang, et al.

Figure 11. Axial PCASL image shows the infarction in the left parietal lobe (white arrow) with the absence of labeled water protons.

labelled by using a RF pulse that saturates rate. The solute protons are always at a very water protons. Subtraction between labelled low concentration and hard to identify directly and control images eliminate the static signals using standard MR protocols. Nonetheless, after and the remaining signals are linear measures a certain time of continuous transfer, this effect to the perfusion, which is corresponding to the alleviates the MRI signal and the protons are Cerebral Blood Flow (CBF). discovered indirectly through the attenuation of the water signal [19,20]. ASL can be indicated in assessment of cerebrovascular stroke, vascular Previous studies manifested that APT MRI is malformation, encephalitis, migraine- sensitive to changes in cellular pH and protein associated, hyperperfusion, hypoperfusion, concentration related to cell proliferation. dementia, migraine, infectious etiologies, Therefore, the APT signal strength indirectly physiologic quantification, posterior reversible reflects the malignant tumor grade. Tumor encephalopathy syndrome, cognitive disorders, grade and APT signal have been noticed to pediatric patients, immunocompromised be generally positively correlated: high-grade patients, patients with GBCE allergy and tumors are tendency to manifest a high APT impaired renal function patients [12,13]. contrast as seen in FIGURE 12. Some studies differentiating tumor grades with APT signal „„APT in glioma suggest that APT can support tumor APT is a new MRI technique not used GBCE grading and separating high-grade from low- which detects endogenous mobile proteins and grade [21-23]. peptides in biotissues. The low-concentration proteins are labelled by saturating their Advantage and disadvantage interchangeable protons such as hydroxyl, amine, The greatest advantage of PWI is the value and amide through selective RF irradiation at of quantitative parameters derived from the their specific resonance frequency, and then sequences reflected the perfusion, permeability the labelled protons are transferred to the bulk and vascularity of tissues compared to water via chemical exchange at an exchange conventional contrast-enhanced T1W. In

76 Imaging Med. (2018) 10(3) Clinical approach of perfusion-weighted imaging SHORT COMMUNICATION

Figure 12. Axial quantitative PWI image shows the glioblastoma multiform in the left occipital lobe (A) T1-weighted image; (B) T2-weighted image; (C) Post-gadolinium T1-weighted image; (D) APT map (E) Algorithm of perfusion weighted imaging techniques. addition, PWI is also the most robust technique method in accessing the tissue perfusion and in recommending the malignant or benign risk permeability. All parameters derived from PWI of tumor, monitoring the response of tumor should be considered carefully by clinicians in to chemotherapy, radiation, and assessing the order to obtain the confident diagnosis and recurrent of disease. Nonetheless, PWI is needed appropriate treatment for patients. to exploit the appropriate dynamic sequences and corresponding computer-aided program Disclosure statement to investigate in comparison with simple Luc Minh Truong is an employee of contrast-enhanced T1W. Currently, novel and Siemens. However, the scientific guarantor innovative PWI sequences and analysis software of this publication is Dr. Nguyen Minh Duc were achieved in order that the clinicians can and Dr Huynh Quang Huy, Department of economize time and cost. In terms of research on Radiology, Pham Ngoc Thach University of the physiological and biological characteristics of Medicine. Nguyen Minh Duc and Huynh tissue, PWI is more predominant and academic Quang Huy contributed equally to this article. than simple contrast-enhanced T1W [1-5]. All authors read and approved the manuscript. Conclusion The authors of this manuscript report no conflict of interest. PWI is one of the most robust and accuracy

Brain Tumor Imaging: What Radiologists Need permeability: Basic concepts and measurement REFERENCES to Know. Korean. J. Radiol. 17, 598-619 (2016). in DCE-CT and DCE-MRI. Diagn. Interv. 1. Essig M, Shiroishi MS, Nguyen TB et al. Imaging. 94, 1187-1204 (2013). Perfusion MRI: The Five Most Frequently Asked 3. Essig M, Nguyen TB, Shiroishi MS et al. Technical Questions. AJR. Am. J. Roentgenol. Perfusion MRI: The Five Most Frequently Asked 5. Jahng GH, Li KL, Ostergaard L et al. Perfusion 200, 24–34 (2013). Clinical Questions. AJR. Am. J. Roentgenol. 201, Magnetic Resonance Imaging: A Comprehensive 495-510 (2013) Update on Principles and Techniques. Korean. J. 2. Kim M, Kim HS. Emerging Techniques in Radiol. 15, 554-577 (2014). 4. Cuenod CA, Balvay D. Perfusion and vascular

Imaging Med. (2018) 10(3) 77 SHORT COMMUNICATION Duc, Huy, Bang, et al.

6. Petrella JR, Provenzale JM. MR Perfusion Imaging in the Human Brain. Radiology. 285, 18. Wong EC, Cronin M, Wu WC et al. Velocity- Imaging of the Brain: Techniques and 914-922 (2017). selective arterial spin labeling. Magn. Reson. Applications. AJR. Am. J. Roentgenol. 175, 207- Med. 55, 1334-1341 (2006). et al. 219 (2000). 12. Pollock JM, Tan H, Kraft RA Arterial spin-labeled MR perfusion imaging: clinical 19. Park JE, Jahng GH, Jeong HK. Amide Proton 7. Kim YS, Kim BG, Rhim H et al. Uterine applications. Magn. Reson. Imaging. Clin. N. Transfer Imaging in Clinics: Basic Concepts fibroids: semiquantitative perfusion MR Am. 17, 315-338 (2009). and Current and Future Use in Brain Tumors imaging parameters associated with the and Stroke. J. Korean. Soc. Radiol. 75, 419-433 et al. intraprocedural and immediate postprocedural 13. Van Osch MJ, Teeuwisse WM, Chen Z (2016). treatment efficiencies of MR imaging-guided Advances in arterial spin labelling MRI methods J. et al. high-intensity focused ultrasound ablation. for measuring perfusion and collateral flow. 20. Wang S, Jarso S, Van Zijl PCM Role Cereb. Blood. Flow. Metab Radiology. 273, 462-471 (2014). . 37, 1–20 (2017). of Amide Proton Transfer (APT)-MRI of Endogenous Proteins and Peptides in Brain et al. 8. Kim YS, Lee JW, Choi CH et al. Uterine 14. Edelman RR, Siewert B, Darby DG Tumor Imaging. Functional. Brain. Tumor. Fibroids: Correlation of T2 Signal Intensity Qualitative mapping of cerebral blood flow and Imaging. 28, 171-181 (2014). with Semiquantitative Perfusion MR Parameters functional localization with echo-planar MR et al. in Patients Screened for MR-guided High- imaging and signal targeting with alternating 21. Togao O, Yoshiura T, Keupp J Amide Radiology Intensity Focused Ultrasound Ablation. radio frequency. . 192, 513-520 proton transfer imaging of adult diffuse gliomas: Neuro. Radiology. 278, 925-935 (2016). (1994). correlation with histopathological grades. Oncol. 16, 441-448 (2014). et al. 9. Keserci B, Duc NM. Magnetic Resonance 15. Detre JA, Leigh JS, Williams DS Perfusion Magn. Reson. Med et al. Imaging Parameters in Predicting the Treatment imaging. . 23, 37-45 (1992). 22. Park KJ, Kim HS, Park JE Added value of Outcome of High-intensity Focused Ultrasound amide proton transfer imaging to conventional 16. Detre JA, Alsop DC. Perfusion magnetic and perfusion MR imaging for evaluating Ablation of Uterine Fibroids With an Immediate resonance imaging with continuous arterial spin Nonperfused Volume Ratio of at Least 90. Acad. the treatment response of newly diagnosed labeling: methods and clinical applications in glioblastoma. Eur. Radiol. 26, 4390-4403 Radiol. 25, 1-8 (2018). Eur. J. Radiol the central nervous system. . 30, (2016). 10. Schuenke P, Paech D, Koehler C et al. Fast and 115-124 (1999). 23. Park JE, Kim HS, Park KJ et al. Pre-and Quantitative T1ρ-weighted Dynamic Glucose 17. Garcia DM, Bazelaire CD, Alsop D. Pseudo- Enhanced MRI. Sci. Rep. 7, 1-10 (2017). Posttreatment Glioma: Comparison of Amide continuous Flow Driven Adiabatic Inversion Proton Transfer Imaging with MR Spectroscopy Intl. Soc. Mag. Reson. 11. Paech D, Schuenke P, Koehler C et al. T1ρ- for Aterial Spin Labeling. for Biomarkers of Tumor Proliferation. Med weighted Dynamic Glucose-enhanced MR . 10, 5 (2005). Radiology. 278, 514 (2016).

78 Imaging Med. (2018) 10(3)