Minimally invasive parathyroidectomy (MIP) has increasingly become the standard of care for surgical treatment of primary hyperparathyroidism over bilateral neck exploration, due decreased morbidity and costs, with similar rates of surgical cure.^1–3 Precise and accurate preoperative localization is critical to the successful performance of MIP, and parathyroid imaging has gone through a series of changes and innovation as a result. Cross-sectional imaging has much to offer this patient population. In this issue of the AJNR News Digest, we highlight the emerging techniques of dynamic contrast-enhanced CT and MR imaging for preoperative localization of parathyroid lesions.

Multiphase multidetector CT for localization of parathyroid adenomas and multigland hyperplasia is also known as 4D-CT (4-dimensional CT), referring to the combination of multiplanar “3-dimensional CT” and the added fourth “dimension” derived from changes in enhancement over time.⁴ Although the vast majority of the literature has focused on 4D-CT^4–11, a few recent studies have outlined a similar approach using MRI.^12–14

4D-CT was first described in the surgical literature in 2006,⁴ and multiple subsequent studies have reported higher sensitivity and accuracy relative to the traditional imaging modalities of technetium Tc99m sestamibi and ultrasonography.^5,6,9,15,16 However, there remains wide variability in the technical protocols used at various institutions¹⁰ and significant concerns regarding radiation exposure.^5,9,10,17,18

There is persistent controversy over the optimum number of phases for 4D-CT. The original protocol included 4 phases: non-contrast-enhanced and 3 contrast-enhanced phases (arterial and 2 delayed venous phases).⁴ A few of the largest retrospective studies reported similar or improved sensitivities and accuracies for 3-phase protocols (noncontrast, arterial, and 1 delayed phase) compared with 4-phase 4D-CT and/or scintigraphy¹⁶ (AJNR 2014;35:176–18). Subsequently, a few papers have argued for 2 or fewer phases,¹⁹ including 2 of the articles selected for this issue (AJNR 2014;35:1959–64, AJNR 2015;36:2373–79). However, these studies were retrospective re-reviews of 4-phase studies, may have been confounded by memory bias, and did not address confidence in reporting lesions on 4D-CT, which can have a significant impact on a surgeon’s decision to perform MIP. At least 2 studies have argued that a 3-phase protocol is the optimum technique for confidently identifying parathyroid lesions preoperatively, based on prediction model performance¹¹ and variability of parathyroid adenoma enhancement patterns, respectively.²⁰ Anecdotally, a 3-phase protocol seems to be the current preferred approach at many large tertiary referral centers and has been described as a favored protocol in at least one “how to” review article.¹⁰

Multiphase imaging raises appropriate concerns regarding radiation exposure. Depending on the protocol, 4D-CT can have an effective dose more than twice that of scintigraphy, and is associated with a markedly higher organ dose to thyroid.^17,18  4D-CT should be used judiciously in young patients.¹⁷ However, estimates of lifetime radiation-induced cancer incidence remain low, and the benefits of increased diagnostic accuracy of 4D-CT likely outweigh the very small attributable risk in the older population, keeping in mind that the average age of disease onset for primary hyperparathyroidism is in the fifth and sixth decades of life.^1,18 4D-CT has also been shown to be more cost-effective than scintigraphy and, if used as a first-line imaging modality, may have the potential for lowering overall radiation dose and costs if additional imaging tests are avoided.^1,18

Dynamic contrast-enhanced MR imaging has the potential to provide similar anatomic detail and perfusion characteristics to 4D-CT, but without ionizing radiation. In the past, MRI was unable to achieve adequate spatial and temporal resolution over the large FOV required for parathyroid imaging; however, a few recent studies have utilized fast imaging techniques such as time-resolved imaging with stochastic trajectories (TWIST) and new fat saturation techniques to overcome these technical limitations¹³ (AJNR 2015;36:2147–52). Although the sample sizes are small, the initial results are promising, with reported diagnostic accuracies and sensitivities equal to or greater than those reported for 4D-CT.^12,14

In summary, the radiologist has much to offer the surgeon and patient contemplating MIP for primary hyperparathyroidism due to recent innovations in parathyroid imaging. 4D-CT combines excellent anatomic detail with perfusion data to provide high confidence for surgical planning,

with higher diagnostic accuracy and sensitivity compared with the traditional imaging modalities of ultrasound and scintigraphy. However, there remains controversy over the optimum number of phases and increased radiation dose to the patient. Recent technical advances have allowed for development of similar dynamic contrast-enhanced MR imaging protocols, with promising results in small study cohorts.

References

1. Lubitz CC, Stephen AE, Hodin RA, et al. Preoperative localization strategies for primary hyperparathyroidism: an economic analysis. Ann Surg Oncol 2012;19:4202–09, 10.1245/s10434-012-2512-2
2. Greene AB, Butler RS, McIntyre S, et al. National trends in parathyroid surgery from 1998 to 2008: a decade of change. J Am Coll Surg 2009;209:332–43, 10.1016/j.jamcollsurg.2009.05.029
3. Beyer TD, Solorzano CC, Starr F, et al. Parathyroidectomy outcomes according to operative approach. Am J Surg 2007;193:368–72, 10.1016/j.amjsurg.2006.09.023
4. Rodgers SE, Hunter GJ, Hamberg LM, et al. Improved preoperative planning for directed parathyroidectomy with 4-dimensional computed tomography. Surgery 2006;140:932–40, 10.1016/j.surg.2006.07.028
5. Mortenson MM, Evans DB, Lee JE, et al. Parathyroid exploration in the reoperative neck: improved preoperative localization with 4D-computed tomography. J Am Coll Surg 2008;206:888–95, 10.1016/j.jamcollsurg.2007.12.044
6. Lubitz CC, Hunter GJ, Hamberg LM, et al. Accuracy of 4-dimensional computed tomography in poorly localized patients with primary hyperparathyroidism. Surgery 2010;148:1129–37, 10.1016/j.surg.2010.09.002
7. Hunter GJ, Schellingerhout D, Vu TH, et al. Accuracy of four-dimensional CT for the localization of abnormal parathyroid glands in patients with primary hyperparathyroidism. Radiology 2012;264:789–95, 10.1148/radiol.12110852
8. Chazen JL, Gupta A, Dunning A, et al. Diagnostic accuracy of 4D-CT for parathyroid adenomas and hyperplasia. AJNR Am J Neuroradiol 2012;33:429–33, 10.3174/ajnr.A2805
9. Cheung K, Wang TS, Farrokhyar F, et al. A meta-analysis of preoperative localization techniques for patients with primary hyperparathyroidism. Ann Surg Oncol 2012; 19:577–73, 10.1245/s10434-011-1870-5
10. Hoang JK, Sung WK, Bahl M, et al. How to perform parathyroid 4D CT: tips and traps for technique and interpretation. Radiology 2014;270:15–24, 10.1148/radiol.13122661
11. Hunter GJ, Ginat DT, Kelly HR, et al. Discriminating parathyroid adenoma from local mimics by using inherent tissue attenuation and vascular information obtained with four-dimensional CT: formulation of a multinomial logistic regression model. Radiology 2014;270:168–75, 10.1148/radiol.13122851
12. Aschenbach R, Tuda S, Lamster E, et al. Dynamic magnetic resonance angiography for localization of hyperfunctioning parathyroid glands in the reoperative neck. Eur J Radiol 2012;81:3371–77, 10.1016/j.ejrad.2012.05.023
13. Grayev AM, Gentry LR, Hartman MJ, et al. Presurgical localization of parathyroid adenomas with magnetic resonance imaging at 3.0 T: an adjunct method to supplement traditional imaging. Ann Surg Oncol 2012;19:981–89, 10.1245/s10434-011-2046-z
14. Merchavy S, Luckman J, Guindy M, et al. 4D MRI for the localization of parathyroid adenoma: a novel method in evolution. Otolaryngol Head Neck Surg 2016;154:446–48, 10.1177/0194599815618199
15. Kukar M, Platz TA, Schaffner TJ, et al. The use of modified four-dimensional computed tomography in patients with primary hyperparathyroidism: an argument for the abandonment of routine sestamibi single-positron emission computed tomography (SPECT). Ann Surg Oncol 2015;22:139–45, 10.1245/s10434-014-3940-y
16. Galvin L, Oldan JD, Bahl M, et al. Parathyroid 4D CT and scintigraphy: what factors contribute to missed parathyroid lesions? Otolaryngol Head Neck Surg 2016 Mar 1. [Epub ahead of print], 10.1177/0194599816630711
17. Mahajan A, Starker LF, Ghita M, et al. Parathyroid four-dimensional computed tomography: evaluation of radiation dose exposure during preoperative localization of parathyroid tumors in primary hyperparathyroidism. World J Surg 2012;36:1335–39, 10.1007/s00268-011-1365-3
18. Hoang JK, Reiman RE, Nguyen GB, et al. Lifetime attributable risk of cancer from radiation exposure during parathyroid imaging: comparison of 4D CT and parathyroid scintigraphy. AJR Am J Roentgenol 2015;204:W579–85, 10.2214/AJR.14.13278
19. Noureldine SI, Aygun N, Walden MJ, et al. Multiphase computed tomography for localization of parathyroid disease in patients with primary hyperparathyroidism: How many phases do we really need? Surgery 2014;156:1300–06, 10.1016/j.surg.2014.08.002
20. Bahl M, Sepahdari AR, Sosa JA, et al. Parathyroid adenomas and hyperplasia on four-dimensional CT scans: three patterns of enhancement relative to the thyroid gland justify a three-phase protocol. Radiology 2015;277:454–62, 10.1148/radiol.2015142393

 

Image modified from: Sepahdari AR, Bahl M, Harari A, et al. Predictors of Multigland Disease in Primary Hyperparathyroidism: A Scoring System with 4D-CT Imaging and Biochemical Markers.