Kazuhiro Tsuchiya, M.D., Masamichi Imai, M.D.

1. Consecutive Acquisition of Time-resolved Contrast-enhanced MRA and Perfusion MR Imaging of Brain Tumors with a Contrast Dose of 16 mL Kazuhiro Tsuchiya, M.D., Masamichi Imai, M.D. Maiko Yoshida, M.D., Hidekatsu Tateishi, M.D., Toshiaki Nitatori, M.D. Department of Radiology, Kyorin University Faculty of Medicine Mitaka, Tokyo, Japan

2. Background In the diagnosis of brain tumors, perfusion MR imaging (PWI) can show tumor hemodynamics closely related to vascularity and tumor grade Aronen HJ, Radiology 1994; Sugahara T, AJR 1994; Knoop EA, Radiology 1999 Time-resolved contrast-enhanced MRA (TCMRA) is another technique that can demonstrate tumor hemodynamics similarly to conventional angiography Yoshikawa T, Eur Radiol 2000; Zou Z, J Magn Reson Imaging 2008 Because of NSF, it is recommended to use a required minimum dose of Gd-based contrast media when its use is indicated

3. Purpose To assess the feasibility and value of consecutive acquisition of PWI and TCMRA in patients with brain tumor in one session using a 16-mL total dose of Gd-based contrast material This dose was chosen as a 17-mL package of a kind of Gd-based contrast agent (ProHance, Bracco, Milan, Italy) is available in our country as well as in many other countries

4. Subjects 28 consecutive patients with brain tumor 14 males and 14 females age range, 28-82 years (average, 61.3 years) - high-grade glioma, 8 pts; low-grade glioma, 1 pt; metastasis, 5 pts; meningioma, 5 pts; lymphoma, 2 pts; others, 2 pts (esthesioneuroblastoma and cavernous hemangioma) - unproven, 5 pts body weight range, 45-82 kg (average, 58.9 kg)

5. Methods-1 (Imaging Technique) MR imager: 1.5-T system (EXCELART Vantage, Toshiba Medical Systems, Tochigi, Japan) Imaging protocol: 1) Conventional precontrast sequences T1WI, T2WI, FLAIR, and DWI 2) TCMRA (3D fast gradient-echo sequence with parallel imaging and an efficient k-space filling method) 3) PWI (gradient-echo echo-planar sequence) 4) Postcontrast T1WI

6. Methods-2 (Imaging Technique) Table 1: Scanning parameters

7. Methods-3 (Imaging Technique) Contrast injection: 8 mL of Gd-based contrast material and 22 mL of flush saline at a rate of 3 mL/sec from an antecubital vein using a power injector for both TCMRA and PWI Image reconstruction: 1) TCMRA: WS and/or MR imager console 2) PWI: WS (AZE Virtual Place)

8. Methods-4 (Image Assessment) • Visual assessment of TCMRA and perfusion maps (rCBF, rCBV, and MTT) • - Grade 1 (poor): tumor was not delineated/contrast with the normal brain was absent (TCMRA/PWI) • - Grade 2 (fair): tumor was delineated but vascularity and adjacent vessels were incompletely visualized/ tumor was delineated but contrast with the normal brain was poor (TCMRA/PWI) • - Grade 3 (good): tumor vascularity and adjacent vessels were clearly depicted/ tumor was depicted with good contrast with the normal brain (TCMRA/PWI) • Determined by consensus of two experienced neuroradiologists

9. Methods-5 (Image Assessment) (2) Information additionally obtained by the two techniques was assessed comparing with the final pathological diagnosis

10. Results-1 (1) Visual assessment of TCMRA and perfusion maps (rCBF, rCBV, and MTT) In all patients, we obtained TCMRA images and three kinds of perfusion maps that allowed assessment of tumor hemodynamics Table 2: Scores of image assessment

11. Results-2 (2) Information additionally obtained by the two techniques Table 3: Comparison between the preoperative Dx and the histological Dxin 23 pts Note,-GBM indicates glioblastoma; AOA, anaplastic oligoastrocytoma

12. Case 1: A 68-year-old man with glioblastoma B C A rCBV (mL/100g) T2-weighted (A) and postcontrast T1-weighted (B) images suggest glioblastoma. rCBV map (C) shows elevated CBV compatible with glioblastoma. TCMRA (D) also shows irregular stain and early venous drainage suggestive of glioblastoma. In this patient, a correct preoperative diagnosis was made without TCMRA or PWI.

13. Case 1: A 68-year-old man with glioblastoma B D A TCMRA T2-weighted (A) and postcontrast T1-weighted (B) images suggest glioblastoma. rCBV map (C) shows elevated CBV compatible with glioblastoma. TCMRA (D) also shows irregular stain and early venous drainage suggestive of glioblastoma. In this patient, a correct preoperative diagnosis was made without TCMRA or PWI.

14. Case 2: A 40-year-old woman with metastasis from breast cancer rCBV (mL/100g) B A C T2-weighted (A) and postcontrast T1-weighted (B) images show a mass in the left parietal lobe that can be metastasis or high-grade glioma. rCBV map (C) shows elevated CBV at marginsofthemassand TCMRA (D) also shows afaint stain. Althoughthepreoperativediagnosiswashigh-gradeglioma,the final diagnosis after surgery was metastasis from breastcancer. In retrospect,findings of TCMRA and PWI may have beensuggestiveofmetastasis.

15. Case 2: A 40-year-old woman with metastasis from breast cancer TCMRA B A D T2-weighted (A) and postcontrast T1-weighted (B) images show a mass in the left parietal lobe that can be metastasis or high-grade glioma. rCBV map (C) shows elevated CBV at marginsofthemassand TCMRA (D) also shows afaint stain. Althoughthepreoperativediagnosiswashigh-gradeglioma,the final diagnosis after surgery was metastasis from breastcancer. In retrospect,findings of TCMRA and PWI may have beensuggestiveofmetastasis.

16. Case 3: An 80-year-old man with metastasis from rectal cancer rCBV (mL/100g) B A C T2-weighted (A) and postcontrast T1-weighted (B) images show ring-like mass in the cerebellar vermis that can be metastasis or high-grade glioma. rCBV map (C) shows slightly elevated CBV at marginsand TCMRA (D) also shows a very faint stain. These findings are suggestive of metastasis. The final diagnosis after surgery was metastasis from rectal cancer. In this patient, a correct diagnosis of metastasis was made with findings of TCMRA and PWI

17. Case 3: An 80-year-old man with metastasis from rectal cancer B A D T2-weighted (A) and postcontrast T1-weighted (B) images show ring-like mass in the cerebellar vermis that can be metastasis or high-grade glioma. rCBV map (C) shows slightly elevated CBV at marginsand TCMRA (D) also shows a very faint stain. These findings are suggestive of metastasis. The final diagnosis after surgery was metastasis from rectal cancer. In this patient, a correct diagnosis of metastasis was made with findings of TCMRA and PWI

18. Discussion-1 Our basic idea was that, if the same amount of contrast material was employed, it was preferable to use it in a manner that could provide more diagnostic information in establishing the diagnosis. In this regard, we confirmed that, by using 8 mL each, consecutive acquisition of TCMRA and PWI could yield images of sufficient diagnostic value As for PWI, it has been reported that, as extravasation of contrast agent due to disruption of the blood-brain barrier occurs in some tumors, the administration of a predose of Gd-based contrast material is effective to prevent artificial lowered estimation of rCBV (Boxermann JL, AJNR 2006). Although there is a study that reported that no significant difference between PWIs with and without a predose (Spampinato MV, Neuroradiology 2006), our study order (TCMRA followed by PWI) may have worked well in this regard

19. Discussion-2 In six of the 23 patients with histological diagnosis (26.1%), TCMRA and/or PWI contributed to the glioma grading or making the differential diagnosis. In 13 patients (56.5%), however, conventional MR findings were sufficient to make the correct diagnosis and no additional information was obtained by TCMRA and/or PWI. Therefore, although in a limited part of the patient group, the two techniques provided valuable additional information in the differential diagnosis without additional contrast administration

20. Conclusion It is possible to consecutively perform TCMRA and PWI in this order using 8 mL each of Gd-based contrast material. The two techniques can provide images that facilitate the preoperative differential diagnosis of brain tumors