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Diffusion Imaging to Characterize Tumor Cellularity - AJNR News Digest
July 2014
Introduction

Diffusion Imaging to Characterize Tumor Cellularity

Asim Choudhri

Asim Choudhri

Diffusion-weighted imaging rose to prominence due to its ability to rapidly detect early signs of cellular metabolic shutdown (cytotoxic edema), and it quickly became the gold standard for the detection of acute cerebral infarction. While DWI is typically evaluated in a qualitative manner, quantified calibrated information can be obtained in the form of apparent diffusion coefficient maps. Further advances in quantification of the direction of motion in diffusion tensor imaging have allowed an important tool for mapping white matter pathways. More recent work evaluating the non-Gaussian properties of water diffusion has resulted in diffusion kurtosis imaging (DKI). Simultaneous with these advances in technology has come a greater appreciation for the information contained in the original diffusion-weighted sequence.

The nuclear-to-cytoplasmic ratio of a tumor tends to correspond to tumor cellularity and grade. To a first approximation, using a rudimentary understanding of histopathology (which is the extent of my knowledge), more purple and less pink on an H&E slide corresponds with more aggressive tumors. Pink areas on H&E correspond to cytoplasm, which has relative facilitated diffusion, and purple areas correspond to the nucleus, which is densely packed and thus has less free water diffusion. Accordingly, a high nuclear-to-cytoplasmic ratio will tend to be associated with reduction in the free diffusion of water molecules as depicted by low ADC values. In this issue of AJNR Digest, we have focused on important articles that use ADC values to attempt to stratify tumor histopathology.

In the article by Rumboldt et al,1 ADC values were evaluated in 32 children with posterior fossa masses. There were statistically differing groupings of ADC values between pilocytic astrocytomas (WHO grade I), ependymoma (WHO grade II), and medulloblastoma (WHO grade IV). On a patient-basis, the pilocytic astrocytoma with the lowest ADC was similar to the ependymoma with the highest ADC. Similarly, the ependymoma with the lowest ADC was similar to the medulloblastoma with the highest ADC. While this was a small series, and there were no anaplastic ependymomas, this important article helped pave the way for diffusion to stratify tumor histology.

Kralik et al2 expanded upon the use of ADC to characterize tumors in 19 children presenting with supratentorial tumors in the first year of life. Given the heterogeneity of histopathologic diagnoses in this group, the authors performed a correlation study between ADC and tumor grade instead of comparing by diagnosis, confirming a negative correlation (ie, low ADC corresponded to high tumor grade).

Toh et al3 applied these techniques to infiltrating cerebral neoplasms in adults, in particular lymphoma and glioblastoma, two entities that are commonly stated to be relatively indistinguishable. ADC values in lymphoma were shown to be lower than those of glioblastoma. Fractional anisotropy was also shown to be lower in lymphoma than glioblastoma in this study that used diffusion tensor imaging.

Dumrongpisutikul et al4 compared ADC values in 20 pineal cell tumors spanning all age groups and showed pineal cell origin tumors had lower ADC values than germinomas. This has significant implications, as germinomas are typically treated by adjunctive therapy as opposed to maximal cytoreductive surgery.

Yeom et al5 used ADC to evaluate 19 patients with central skull base chordomas and chondrosarcomas, a pair of entities that has also classically been stated to be radiologically indistinguishable. Chordomas were shown to have significantly lower ADC values than chondrosarcoma, with the lowest ADC values in poorly differentiated chordomas.

Eida et al6 performed ADC analysis of 31 patients with salivary gland tumors, showing that ADC values were higher in benign tumors than malignant tumors. A cutoff of 1.8 x 10-3 mm2/sec was used to stratify tumors into benign or malignant with a 97% accuracy, 100% positive predictive value, and 96% negative predictive value.

The use of DWI and ADC in the evaluation of neoplasms can provide secondary information about the microstructural characteristics of a lesion. By extending evaluation beyond structure, this can aid in prediction of lesion histology. Further work will establish the generalizability of these results across different MRI vendors, age groups, and risk factors, as applied to larger populations. While imaging may not be able to replace tissue sampling (at least until there are further advances in molecular imaging and in vivo tagging), appropriate use of this commonly used technique can help stratify lesions, possibly aiding in surgical planning.

ADC is by no means the only noninvasive technique to stratify tumor aggressiveness. However, MR spectroscopy takes time and can be difficult to interpret. Perfusion imaging can be complicated to acquire and process and remains relatively qualitative. Future work, hopefully, can evaluate the predictive power of multiple noninvasive parameters, possibly in conjunction with clinical data (such as germ cell markers for pineal tumors), to create a more robust predictor model.

Many radiologists may not be familiar with quantitative ADC analysis; however, this sequence is likely already acquired with a majority of MRI examinations and can be used in conjunction with other techniques. As we learn more about this powerful (yet seemingly simple) sequence, it is appropriate to provide guidance to facilitate more routine clinical adoption.

References

  1. Rumboldt Z, Camacho DLA, Lake D, et al. Apparent diffusion coefficients for differentiation of cerebellar tumors in children. AJNR Am J Neuroradiol 2006;27:1362–69
  2. Kralik SF, Taha A, Kamer AP, et al. Diffusion imaging for tumor grading of supratentorial brain tumors in the first year of life. AJNR Am J Neuroradiol, 2013 November 7 [Epub ahead of print], 10.3174/ajnr.A3757
  3. Toh CH, Castillo M, Wong AMC, et al. Primary cerebral lymphoma and glioblastoma multiforme: differences in diffusion characteristics evaluated with diffusion tensor imaging. AJNR Am J Neuroradiol 2008;29:471–75, 10.3174/ajnr.A0872
  4. Dumrongpisutikul N, Intrapiromkul J, Yousem DM. Distinguishing between germinomas and pineal cell tumors on MR imaging. AJNR Am J Neuroradiol 2012;33:550–55, 10.3174/ajnr.A2806
  5. Yeom KW, Lober RM, Mobley BC, et al. Diffusion-weighted MRI: distinction of skull base chordoma from chondrosarcoma. AJNR Am J Neuroradiol 2013;34:1056–61, 10.3174/ajnr.A3333
  6. Eida S, Sumi M, Sakihama N, et al. Apparent diffusion coefficient mapping of salivary gland tumors: prediction of the benignancy and malignancy. AJNR Am J Neuroradiol 2007;28:116–21

 

Image modified from: Eida S, Sumi M, Sakihama N, et al. Apparent diffusion coefficient mapping of salivary gland tumors: prediction of the benignancy and malignancy.