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Reproducibility of quantitative CT perfusion imaging

Departments of ¹Radiology, ²Oncology and ³Neurosurgery, Addenbrooke's Hospital and the University of Cambridge, Cambridge CB2 2QQ, UK

	Abstract

Top Abstract Introduction Materials and methods Results Discussion Conclusion References

 
The ability to demonstrate regions of abnormal cerebral blood flow in the setting of acute stroke is of diagnostic and prognostic importance. It may also influence therapeutic strategies. The advantage of CT perfusion imaging is its ability to give quantifiable measurements of cerebral blood flow on any modern CT machine without the need to buy specialized equipment. The aim was to assess day-to-day variability of values of cerebral blood volume obtained with this technique. Seven patients with cerebral gliomas were studied using dynamic CT perfusion imaging on two occasions, approximately 24 h apart to reduce variability from diurnal variations. Regions of interest were produced in predominately middle cerebral artery locations in both hemispheres on the first and second CT perfusion studies. Absolute values for cerebral blood flow were produced for these regions and were correlated with flows obtained in the same regions of interest on the follow-up study. The Pearson correlation coefficient obtained was 0.884. CT perfusion imaging is easily performed on conventional modern CT equipment and demonstrates little variability in measures of absolute cerebral blood flow within individuals when studied on two occasions within 24 h.

	Introduction

Top Abstract Introduction Materials and methods Results Discussion Conclusion References

 
The advent of possible therapeutic strategies in acute stroke has increased the need for a simple, quick, reliable and effective method of assessing cerebral blood flow that is practicable in any hospital admitting patients with acute stroke. Unfortunately, techniques such as xenon CT and positron emission tomography (PET) are relatively complex and are only available in a few centres, precluding their generalized use in acute stroke. Quantitative MR perfusion techniques are available [1], although there are possible problems regarding absolute quantification and 24 h availability of imaging facilities.

Miles et al recently developed a single slice quantifiable CT technique using changes in attenuation within the aorta as an input function [2], a technique that has been used in the assessment of renal [3] and hepatic [4] perfusion. We have previously reported on the refinement of this technique to measure cerebral blood flow using venous drainage into the sagittal sinus as a surrogate input function [5], a methodology that is currently being used to assess acute stroke patients [6]. The aim of this study was to evaluate the robustness of the technique by assessing the day-to-day reproducibility of the methodology.

	Materials and methods

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Seven male patients (mean age 53 years, range 43–72 years) with gliomas, who were due to startradiotherapy, were evaluated with CT perfusion imaging on two occasions, 24 h apart. Approval was obtained from the LocalResearch Ethics Committee of Addenbrooke's Hospital andall patients gave fully informed consent. Before dynamic imaging, conventional CT imagesof the brain were obtained on a GE HiSpeed Advantage machine (General Electric, Milwaukee, WI) using contiguous slice thicknesses of 10 mm. This part of the study represented part of the routine planning CT. A single 10 mm slice was then chosen from the pre-contrast study, taking care to avoid the orbits. If possible, the slice was chosen away from any CT-demonstrated abnormality. A 50 ml bolus ofiopamidol (300 mg I ml^-1, Niopam; E Merck Pharmaceutical, Middlesex, UK) was injected using a power injector (Injektron 85; Medizinische Systeme GmBH, Saarbrucken, Germany) via anantecubital vein at a rate of 5 ml s^-1. The CT imaging sequence was begun immediately at the start of bolus injection. The first data acquisition was obtained 6.5 s after the start of bolus injection. Subsequent CT acquisitions were obtained at 2 s intervals for 12 s, and then 4 s intervals for a further 12 s. Thus, CT data were acquired intermittently for 30.5 s. Conventional enhanced CT images were then obtained of the whole brain. The patient's head was then marked with ink in five places using the sagittal midline and coronal plane CT guidance lasers to facilitate co-registration. Each patient was re-imaged at 24 h using an identical gantry angle orientating the patient's head to the pre-defined marks. The CT perfusion sequence was run again.

A maximum enhancement image was obtained for each pixel over serial slices, which generated a composite image that identified the principal arterial and venous structures. This technique uses previously defined pre-set time density limit curves for vessels (minimum -5 Hounsfield units (HU), maximum 400 HU). A region of interest was then drawn around the sagittal sinus and was used as the "input" function. The methodology is based on previous work of Leggett et al [7] where, using the indicator dye–dilution theory, tissue perfusion is given by the formula:

A CT perfusion image was then obtained using an algorithm that excluded large vessels. This produced measures of absolute cerebral blood flow on a pixel-by-pixel basis for all the brain in the imaged slice. Regions of interest were drawn predominately in the middle cerebral artery territories and an average cerebral blood flow value was obtained for each region. The same region of interest was selected on the follow-up CT study and each composite region of interest was compared with that obtained on the second study, comparing the values obtained for the same hemisphere. Correlation coefficients and other analyses were calculated using SPSS^TM (SPSS Inc, Chicago, IL).

	Results

Top Abstract Introduction Materials and methods Results Discussion Conclusion References

 
All studies were performed without complication. The mean interval between studies was 24 h 28 min (range 23 h 8 min to 25 h 57 min). Figure 1 demonstrates a representative CT perfusion image of patient No. 4. The scatter plot of the CT perfusion values obtained on day 1 and day 2 are reproduced in Figure 2. The Pearson correlation coefficient comparing the values obtained on day 1 and day 2 was 0.884. Regions of interest measured 1155±249 pixels (mean±standard deviation). None of the regions of interest included CT-identifiable abnormal tissue. In two patients, tumour was included on the imaged slice, and a further patient had an area of oedema included. The algorithm for excluding blood vessels resulted in 78.3±3.6% actual pixels in each region of interest being included in the analysis.

View larger version (28K): [in this window] [in a new window]   Figure 1. Conventional CT demonstrating the region of interest over the sagittal sinus that is used as the inputfunction. Representative regions of interest in the middle cerebral arteries are also shown. The associated quantitative CT perfusion image is also shown.

View larger version (11K): [in this window] [in a new window]   Figure 2. Scatter plot of cerebral blood flow values obtained from regions of interest in both cerebral hemispheres for the seven volunteers.

	Discussion

Top Abstract Introduction Materials and methods Results Discussion Conclusion References

The possible importance of this technique is the ability to use it on almost any modern CT machine without the need for specialist equipment. Even the intravenous pump is not essential, although it is desirable [4]. Conventional CT is less sensitive that MR in the demonstration of acute non-haemorrhagic stroke [10], although it is used in therapeutic trials for early stroke mainly owing to its generalized availability and implicit sensitivity to acute haemorrhage [11].

The demonstration of areas of abnormal cerebral blood flow using CT perfusion in patients with acute stroke who may have a normal conventional CT study could be of great diagnostic and therapeutic use. Although this is an area of tremendous progress in MR [12], the lack of widespread 24 h availability of MR precludes its generalized use in acute stroke. CT perfusion imaging is now being used in the routine assessment of acute stroke [13], and has been shown to be particularly valuable in the identification of reversible ischaemia [13]. The technique may prove to be an alternative, reliable and available diagnostic strategy in acute stroke, especially if used on machines capable of multislice imaging.

	Conclusion

Top Abstract Introduction Materials and methods Results Discussion Conclusion References

 
CT perfusion imaging is easily performed and demonstrates little variability within individuals when studied on two occasions within 24 h. This study further supports the use of this simple, robust and reliable technique in studies of brain perfusion.

	Acknowledgments

 
Mike Hayball developed the CT perfusion analysis software. The help of the neuroradiographers is greatly appreciated.

	Footnotes

 
Funded by a Pump Primer Grant of the Royal College of Radiologists.

Received for publication October 10, 2000. Revision received January 24, 2001. Accepted for publication March 20, 2001.

	References

Top Abstract Introduction Materials and methods Results Discussion Conclusion References

 

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