RE: Contrast-enhanced T1-Weighted 3D FSE SPACE Sequence Demonstrates Improved Detection of Brain Metastasis Over 3D GRE-Based FLASH at 3T
Ramona A.Todea, Neuroradiologist, Department of Neuroradiology University Hospital Zurich, Switzerland
21 April 2025
Cerebral metastatic disease is the most common malignancy of the central nervous system, with over 100,000 new cases diagnosed annually in the United States1 2. Early detection is essential, enabling timely intervention and improving patient quality of life. Accurate identification of brain metastases is critical, as treatment options—including stereotactic radiosurgery (SRS)3, whole-brain radiation therapy, or systemic therapy—depend on the number and size of lesions. Contrast-enhanced (CE) T1-weighted 3D MRI remains the standard for detecting and delineating brain metastases. However, the optimal CE T1-weighted sequence remains a subject of investigation.
Magnetization-prepared rapid acquisition with gradient echo (MP-RAGE), a gradient recalled-echo (GRE)-based sequence, is widely used for its excellent gray-white matter contrast and high spatial resolution. However, GRE-based sequences like MP-RAGE provide lower contrast enhancement than spin-echo (SE) sequences, making metastases less conspicuous against bright white matter4. In contrast, SE-based sequences such as 3D Sampling Perfection with Application optimized Contrasts using different flip angle Evolution (SPACE) exhibit lower white matter signal intensity—partly due to magnetization transfer effects 5—enhancing lesion conspicuity. Inversion recovery -prepared 3D GRE (IR 3D GRE) sequences produce prominent enhancement of cortical vessels ("bright blood"), which can complicate differentiation between small metastases and vasculature. SE-based sequences like SPACE, with inherent flow suppression, reduce vascular signal, improving visibility of small peripheral metastases.
Prior studies have shown that the 3D SPACE sequence outperforms IR 3D GRE sequences, including MP-RAGE, for detecting small metastatic lesions at 3T5,6. However, limited evidence exists comparing SPACE with non–IR-prepared 3D GRE sequences such as 3D fast low-angle shot (FLASH)7 8.
The current study, “Diagnostic Confidence of Contrast-Enhanced T1-Weighted MRI for the Detection of Brain Metastases: 3D FSE- vs. 3D GRE-Based Sequences” by Maria Gule-Monroe et al., assessed the diagnostic value of CE T1-weighted 3D fast spin-echo (FSE)-based SPACE versus 3D GRE-based FLASH for brain metastasis detection using 3T MRI in a cohort of 72 patients. Key metrics included the number of metastatic and indeterminate lesions, lesion margins, contrast-to-noise ratio (CNR), image artifacts, and overall image quality. Additionally, CNR was quantified for solidly enhancing lesions >1 cm.
The study showed that the SPACE sequence detected more lesions than 3D FLASH and identified fewer indeterminate lesions. Assessment of lesion margins, CNR, and image quality—rated on a Likert scale—demonstrated significantly better performance with SPACE, including fewer artifacts (p < 0.00001). Inter-reader lesion detection concordance, measured by Krippendorff’s alpha, was higher for SPACE (0.962) than for 3D FLASH (0.870), or the combined sequences (0.918).
This is the first study to directly demonstrate the superior performance of SPACE over a non–IR-prepared 3D GRE sequence in detecting CE metastatic lesions in a sizable cohort. Although the CNR result from qualitative assessment significantly differed between sequences, the difference in quantitative CNR did not reach statistical significance—likely due to the small sample size (n = 16) or to a small CNR difference, like findings by Danieli et al.9 . Fewer indeterminate lesions likely reflect the suppression of vascular enhancement in SPACE, a factor correlated with increased diagnostic confidence. The sequence suppresses flow-related signal due to intravoxel dephasing and stimulated echoes from variable flip-angle radiofrequency pulses10, allowing more confident attribution of enhancement to metastases. Improved lesion margin delineation with SPACE is particularly relevant for SRS planning, where both detection and accurate contouring are essential. While this study did not compare the volume of the lesions detected, a previous study9 showed significantly larger lesion volumes with SPACE compared to MP-RAGE. No significant difference in interpretation time was found, though there was a trend toward longer reading with SPACE, possibly due to reader unfamiliarity with the sequence or higher lesion counts.
Limitations of SPACE include reduced gray-white matter contrast and suppression of vascular enhancement, which may be less favorable for surgical planning. SE imaging may also produce ghosting artifacts, particularly in the posterior fossa from dural venous sinuses. Additionally, as with prior studies, this one focused solely on 3T MRI systems. Given lower signal-to-noise ratio of SPACE sequence at 1.5T, further research is warranted to evaluate its performance at lower field strengths.
In conclusion, the CE T1-weighted SPACE sequence demonstrated superior performance over 3D FLASH at 3T in detecting brain metastases, with improved image quality, better lesion margin delineation, and fewer indeterminate findings. These results not only support the growing clinical preference for CE 3D spin-echo techniques but also reinforce current consensus recommendations10 that position 3D FSE sequences such as SPACE as the ideal protocol for brain metastasis imaging at 3T.
REFERENCES
1. Nayak L, Lee EQ, Wen PY. Epidemiology of brain metastases. Curr Oncol Rep 2012;14:48-54
2. Tabouret E, Chinot O, Metellus P, et al. Recent trends in epidemiology of brain metastases: an overview. Anticancer Res 2012;32:4655-4662
3. DiLuna ML, King JT, Jr., Knisely JP, Chiang VL. Prognostic factors for survival after stereotactic radiosurgery vary with the number of cerebral metastases. Cancer 2007;109:135-145
4. Furutani K, Harada M, Mawlan M, Nishitani H. Difference in enhancement between spin echo and 3-dimensional fast spoiled gradient recalled acquisition in steady state magnetic resonance imaging of brain metastasis at 3-T magnetic resonance imaging. J Comput Assist Tomogr 2008;32:313-319
5. Kato Y, Higano S, Tamura H, et al. Usefulness of contrast-enhanced T1-weighted sampling perfection with application-optimized contrasts by using different flip angle evolutions in detection of small brain metastasis at 3T MR imaging: comparison with magnetization-prepared rapid acquisition of gradient echo imaging. AJNR Am J Neuroradiol 2009;30:923-929
6. Kwak HS, Hwang S, Chung GH, et al. Detection of small brain metastases at 3 T: comparing the diagnostic performances of contrast-enhanced T1-weighted SPACE, MPRAGE, and 2D FLASH imaging. Clin Imaging 2015;39:571-575
7. Nagao E, Yoshiura T, Hiwatashi A, et al. 3D turbo spin-echo sequence with motion-sensitized driven-equilibrium preparation for detection of brain metastases on 3T MR imaging. AJNR Am J Neuroradiol 2011;32:664-670
8. Park J, Kim J, Yoo E, et al. Detection of small metastatic brain tumors: comparison of 3D contrast-enhanced whole-brain black-blood imaging and MP-RAGE imaging. Invest Radiol 2012;47:136-141
9. Danieli L, Riccitelli GC, Distefano D, et al. Brain Tumor-Enhancement Visualization and Morphometric Assessment: A Comparison of MPRAGE, SPACE, and VIBE MRI Techniques. AJNR Am J Neuroradiol 2019;40:1140-1148
10. Kaufmann TJ, Smits M, Boxerman J, et al. Consensus recommendations for a standardized brain tumor imaging protocol for clinical trials in brain metastases. Neuro Oncol 2020;22:757-772
Cerebral metastatic disease is the most common malignancy of the central nervous system, with over 100,000 new cases diagnosed annually in the United States1 2. Early detection is essential, enabling timely intervention and improving patient quality of life. Accurate identification of brain metastases is critical, as treatment options—including stereotactic radiosurgery (SRS)3, whole-brain radiation therapy, or systemic therapy—depend on the number and size of lesions. Contrast-enhanced (CE) T1-weighted 3D MRI remains the standard for detecting and delineating brain metastases. However, the optimal CE T1-weighted sequence remains a subject of investigation.
Magnetization-prepared rapid acquisition with gradient echo (MP-RAGE), a gradient recalled-echo (GRE)-based sequence, is widely used for its excellent gray-white matter contrast and high spatial resolution. However, GRE-based sequences like MP-RAGE provide lower contrast enhancement than spin-echo (SE) sequences, making metastases less conspicuous against bright white matter4. In contrast, SE-based sequences such as 3D Sampling Perfection with Application optimized Contrasts using different flip angle Evolution (SPACE) exhibit lower white matter signal intensity—partly due to magnetization transfer effects 5—enhancing lesion conspicuity. Inversion recovery -prepared 3D GRE (IR 3D GRE) sequences produce prominent enhancement of cortical vessels ("bright blood"), which can complicate differentiation between small metastases and vasculature. SE-based sequences like SPACE, with inherent flow suppression, reduce vascular signal, improving visibility of small peripheral metastases.
Prior studies have shown that the 3D SPACE sequence outperforms IR 3D GRE sequences, including MP-RAGE, for detecting small metastatic lesions at 3T5,6. However, limited evidence exists comparing SPACE with non–IR-prepared 3D GRE sequences such as 3D fast low-angle shot (FLASH)7 8.
The current study, “Diagnostic Confidence of Contrast-Enhanced T1-Weighted MRI for the Detection of Brain Metastases: 3D FSE- vs. 3D GRE-Based Sequences” by Maria Gule-Monroe et al., assessed the diagnostic value of CE T1-weighted 3D fast spin-echo (FSE)-based SPACE versus 3D GRE-based FLASH for brain metastasis detection using 3T MRI in a cohort of 72 patients. Key metrics included the number of metastatic and indeterminate lesions, lesion margins, contrast-to-noise ratio (CNR), image artifacts, and overall image quality. Additionally, CNR was quantified for solidly enhancing lesions >1 cm.
The study showed that the SPACE sequence detected more lesions than 3D FLASH and identified fewer indeterminate lesions. Assessment of lesion margins, CNR, and image quality—rated on a Likert scale—demonstrated significantly better performance with SPACE, including fewer artifacts (p < 0.00001). Inter-reader lesion detection concordance, measured by Krippendorff’s alpha, was higher for SPACE (0.962) than for 3D FLASH (0.870), or the combined sequences (0.918).
This is the first study to directly demonstrate the superior performance of SPACE over a non–IR-prepared 3D GRE sequence in detecting CE metastatic lesions in a sizable cohort. Although the CNR result from qualitative assessment significantly differed between sequences, the difference in quantitative CNR did not reach statistical significance—likely due to the small sample size (n = 16) or to a small CNR difference, like findings by Danieli et al.9 . Fewer indeterminate lesions likely reflect the suppression of vascular enhancement in SPACE, a factor correlated with increased diagnostic confidence. The sequence suppresses flow-related signal due to intravoxel dephasing and stimulated echoes from variable flip-angle radiofrequency pulses10, allowing more confident attribution of enhancement to metastases. Improved lesion margin delineation with SPACE is particularly relevant for SRS planning, where both detection and accurate contouring are essential. While this study did not compare the volume of the lesions detected, a previous study9 showed significantly larger lesion volumes with SPACE compared to MP-RAGE. No significant difference in interpretation time was found, though there was a trend toward longer reading with SPACE, possibly due to reader unfamiliarity with the sequence or higher lesion counts.
Limitations of SPACE include reduced gray-white matter contrast and suppression of vascular enhancement, which may be less favorable for surgical planning. SE imaging may also produce ghosting artifacts, particularly in the posterior fossa from dural venous sinuses. Additionally, as with prior studies, this one focused solely on 3T MRI systems. Given lower signal-to-noise ratio of SPACE sequence at 1.5T, further research is warranted to evaluate its performance at lower field strengths.
In conclusion, the CE T1-weighted SPACE sequence demonstrated superior performance over 3D FLASH at 3T in detecting brain metastases, with improved image quality, better lesion margin delineation, and fewer indeterminate findings. These results not only support the growing clinical preference for CE 3D spin-echo techniques but also reinforce current consensus recommendations10 that position 3D FSE sequences such as SPACE as the ideal protocol for brain metastasis imaging at 3T.
REFERENCES
1. Nayak L, Lee EQ, Wen PY. Epidemiology of brain metastases. Curr Oncol Rep 2012;14:48-54
2. Tabouret E, Chinot O, Metellus P, et al. Recent trends in epidemiology of brain metastases: an overview. Anticancer Res 2012;32:4655-4662
3. DiLuna ML, King JT, Jr., Knisely JP, Chiang VL. Prognostic factors for survival after stereotactic radiosurgery vary with the number of cerebral metastases. Cancer 2007;109:135-145
4. Furutani K, Harada M, Mawlan M, Nishitani H. Difference in enhancement between spin echo and 3-dimensional fast spoiled gradient recalled acquisition in steady state magnetic resonance imaging of brain metastasis at 3-T magnetic resonance imaging. J Comput Assist Tomogr 2008;32:313-319
5. Kato Y, Higano S, Tamura H, et al. Usefulness of contrast-enhanced T1-weighted sampling perfection with application-optimized contrasts by using different flip angle evolutions in detection of small brain metastasis at 3T MR imaging: comparison with magnetization-prepared rapid acquisition of gradient echo imaging. AJNR Am J Neuroradiol 2009;30:923-929
6. Kwak HS, Hwang S, Chung GH, et al. Detection of small brain metastases at 3 T: comparing the diagnostic performances of contrast-enhanced T1-weighted SPACE, MPRAGE, and 2D FLASH imaging. Clin Imaging 2015;39:571-575
7. Nagao E, Yoshiura T, Hiwatashi A, et al. 3D turbo spin-echo sequence with motion-sensitized driven-equilibrium preparation for detection of brain metastases on 3T MR imaging. AJNR Am J Neuroradiol 2011;32:664-670
8. Park J, Kim J, Yoo E, et al. Detection of small metastatic brain tumors: comparison of 3D contrast-enhanced whole-brain black-blood imaging and MP-RAGE imaging. Invest Radiol 2012;47:136-141
9. Danieli L, Riccitelli GC, Distefano D, et al. Brain Tumor-Enhancement Visualization and Morphometric Assessment: A Comparison of MPRAGE, SPACE, and VIBE MRI Techniques. AJNR Am J Neuroradiol 2019;40:1140-1148
10. Kaufmann TJ, Smits M, Boxerman J, et al. Consensus recommendations for a standardized brain tumor imaging protocol for clinical trials in brain metastases. Neuro Oncol 2020;22:757-772