To the best of the authors’ knowledge, this is the first in-vitro study describing the imaging characteristics of xanthine stones on CT with multiple different energy levels, US and MRI. A previous in-vivo study of xanthine stones using conventional single energy CT showed CT numbers of stones ranging from 276-480 HU . Previous in-vivo US studies have shown xanthine stones to be echogenic with posterior acoustic shadowing, with features identical to other urinary calculi . No previous studies have described the imaging characteristics of xanthine stones on MRI.
On the four different energy levels on CT, in-vitro xanthine stones had an average CT number of 321.4-331.0 HU. There was no significant difference in the measured HU when imaging at different energies (80, 100, 120 and 140 kVp). On the two in-vivo imaging studies performed prior to stone passage xanthine stones had an average CT number of 304-383 HU. These in-vitro and in-vivo numbers are similar to CT numbers reported in the aforementioned in-vivo study of xanthine stones that used conventional single energy CT.
Interestingly, xanthine stones have relatively lower CT numbers than most urinary calculi. For example, reported mean CT numbers for struvite stones are 401-871 HU, cystine stones are 248-1088 HU, calcium oxalate stones are 865-1039 HU, and calcium phosphate stones are 1417 HU [6-8]. Xanthine stones have similar mean CT numbers to uric acid stones, which have reported CT numbers ranging from 270-519 [6, 8]. This may not be surprising given that xanthine and uric acid are part of the same metabolic pathway. The lower density of xanthine stones likely explains the previous literature describing them as radiolucent on radiographs. The lower density makes them more difficult to appreciate on radiographs than other more dense calculi, and stones were likely radiographically occult rather than truly radiolucent.
On in-vitro and in-vivo US, all xanthine stones were echogenic, showed posterior acoustic shadowing, and demonstrated twinkle artifact with color Doppler imaging. These features are identical to other types of urinary stones. Previous in-vivo analyses of xanthine stones have also showed them to be indistinguishable from other urinary stones on US [1-3] Based on these findings, ultrasound is equally suitable to evaluate xanthine stones as any other type of urinary stone.
Xanthine stones showed no signal on all in-vitro MRI sequences tested, including UTE MRI sequences. Stones are expected to result in signal voids on conventional MRI sequences, but recent studies of UTE imaging have shown signal within other types of urinary calculi on UTE sequences [9, 10]. This has led some to suggest that these sequences might be utilized to evaluate urolithiasis. Our analysis suggests that xanthine stones are unlikely to be well visualized when utilizing the described MRI techniques in a clinical setting, including UTE sequences.
Although xanthine urolithiasis is a rare condition, it may cause recurrent symptoms in patients with Lesch-Nyhan Syndrome on allopurinol therapy and in patients with hereditary xanthinuria. Children with Lesch-Nyhan Syndrome are developmentally delayed and are often unable to appropriately verbalize their symptoms, making imaging particularly important in the clinical assessment of these patients. Given the recurrent nature of this condition, multiple imaging studies may be needed over the course of a lifetime. While our study examined rare xanthine stones from a single patient, thus perhaps limiting generalizability, we believe that based on the results of this study, xanthine stones are easily detectable on US. Therefore, US may be the first line imaging test in the evaluation of xanthine stones given its lack of ionizing radiation and ability to visualize these stones. Recent developments in UTE MRI sequences have suggested that MRI may provide an additional imaging modality to assess urinary calculi without ionizing radiation. However, our in-vitro analysis suggests that xanthine stones are not easily detectable on MRI, including UTE sequences, and MRI is unlikely to be helpful in the evaluation of xanthine urolithiasis. Unfortunately, no in-vivo MRI imaging of the stones was performed on this patient prior to stone passage. Our analysis suggests that xanthine stones are well visualized on CT. Therefore, judicious use of conventional non-contrast CT may be appropriate in patients with xanthine urolithiasis when ultrasound is inconclusive or insufficient. The risks of radiation exposure should always be considered, especially given the recurrent nature of this condition and the potential need for multiple imaging studies over a lifetime.
A limitation of our study stems from the small size of xanthine stones on in-vitro analysis. Stones smaller than 5mm in diameter tend to demonstrate lower CT numbers regardless of composition secondary to partial-volume effects. CT numbers in our in-vitro analysis may be lower given the smaller size of the stones studied. However, on in-vivo analysis, prior to stone passage, the stones were as large as 10mm and had comparable CT numbers to that of our in-vitro analysis. This may perhaps partially negate the effect of volume averaging on our in-vitro findings. Previous MRI studies that were able to demonstrate signal within urinary stones used stones larger than 1cm, which is larger than the stones evaluated in this study [7, 10, 11]. This small size may have contributed to the lack of signal seen on all MRI sequences tested in our study. Future studies could benefit from analyzing larger stones, if available.