The Optimal Timing of Hydrogel Injection for Treatment of Intervertebral Disc Degeneration

Quantitative Analysis Based on T1p MR Imaging

Zhiguo Liu, MD; Jianwen Li, MD; Minghsien Hu, MD; Xiaoshuai Wang, MD; Ningning Chen, MD, PhD; Shangbin Cui, PhD; Songbo Li, MD; Hanzhong Liu, MD; Guoliang Chen, MD; Ximin Pan, MD; Haixing Sun, BS; Shaoyu Liu, MD; Fuxin Wei, MD, PhD

Disclosures

Spine. 2020;45(22):E1451-E1459. 

In This Article

Abstract and Introduction

Abstract

Study Design: Animal experimental study.

Objective: The aim of this study was to investigate the optimal time of hydrogel injection for regenerating intervertebral disc degeneration (IDD) based on T1ρ magnetic resonance imaging (MRI).

Summary of Background Data: Currently, different approaches are being pursued to regenerate the IDD. However, the optimal timing for the regenerative intervention is unclear.

Methods: The slowly, progressive IDD models were established in 18 rhesus monkeys. On the basis of the MR T1ρ values of the discs, the rhesus monkeys were divided into severe (T1ρ values: <81 ms), moderate (T1ρ values: 81~95 ms), and mild (T1ρ values: 96~110 ms) degeneration groups. Biocompatible hydrogel was injected into the central part of the nucleus pulposus of the discs under fluoroscopic guidance. Treatment effects were investigated using radiography, T1ρ MRI, and histology until 12 months postoperatively.

Results: After injection, the T1ρ values of all the discs increased significantly at 1 month postoperatively, and then remained at approximately 110 ms in the mild and moderate groups during the whole observation period, with no significant difference compared to the values at 1 month (P > 0.05). However, in the severe group, the T1ρ values decreased significantly after 1 month and leveled at approximately 70 ms after 6 months, with significant difference compared to the values at 1 month (P < 0.05). In the mild and moderate groups, there were no significant differences between preoperative histological scores and those at 12 months (P > 0.05). However, the histological score in the severe group at 12 months was significantly higher than the preoperative scores (P < 0.05).

Conclusion: This study suggested that the moderate degenerative stage of IDD (T1ρ values from 95 to 80 ms) could be the optimal time for hydrogel injection aimed at the regenerative intervention, based on T1ρ-MR imaging technique and quantitative analysis.

Level of Evidence: N/A

Introduction

There are many methods available for the treatment of degenerative disc disease (DDD), including physical therapy in the early stages and discectomy in the late stages.[1] Although treatments like physical therapy may relieve the symptoms, they do not eliminate the cause or stop progression of disc degeneration. Consequently, many patients will ultimately require definitive treatment, that is, spinal fusion.[2]

Spinal fusion, although effective, is associated with significant morbidity. To address this issue, research has identified many promising biological therapies such as gene therapy, stem cell therapy, and the administration of cytokines which may be able to regenerate intervertebral discs.[2–4] The potential for intervertebral disc regeneration is promising; however, the optimal timing for regeneration of degenerative discs is not clear. It is clear that regeneration methods cannot be used in cases of severe intervertebral disc degeneration (IDD) when there is complete loss of the intervertebral space and/or irreversibly damage to facet joints. What is not clear is the degree of degeneration that can be reversed. Therefore, it is important to develop a precise, simple, reproducible diagnostic system to detect the time window of time for biological intervention for the treatment of IDD.

Methods for classifying IDD include histological examination,[5] gross morphological exmaination,[6] and magnetic resonance imaging (MRI).[7,8] Unlike pathological examination, which is generally recognized as the criterion standard for classifying the degree of disc degeneration, neither histological or gross morphological examination is recognized as an accepted method of classification due to the anatomic and physiopathological characteristics of IDD.[9] In contrast, the Modic and Pfirrmann grading systems, which are based on MRI, are both widely used. The Modic classification is based on signal intensity changes in the vertebral body adjacent to the endplates, and has been confirmed by histological studies.[7,10] The Pfirrmann classification is based on magnetic resonance (MR) signal intensity, disc structure, the distinction between nucleus and annulus, and disc height, and was developed with a cohort of symptomatic patients with a mean age of 40 years.[8] The grading system was modified by Griffith et al,[11] who tested the reliability of the modified grading system by analysis of lumbar spine MR images of 260 consecutive intervertebral discs in 52 patients with a mean age of 73 years. However, the aforementioned classifications are based on subjective judgments, which may not appropriately guide the diagnosis and intervention of the early IDD.

The recent development of molecular imaging techniques has allowed the molecular changes of disease to be detected in vivo. Current molecular imaging techniques include gadolinium-enhanced MR imaging,[12] sodium MR imaging,[13] T1ρ- and T2-mapping MR techniques.[14,15] The development of T1ρ MR imaging has been shown to be useful for the molecular diagnosis of IDD, especially in the early stage. Blumenkrantz et al[15] studied early-stage IDD, and reported a close correlation between T1ρ values and clinical symptoms. These initial studies showed that T1ρ-MR imaging and analysis are useful for the early diagnosis of IDD. Zhang et al[16] reported that they used T1ρ relaxation MRI to investigate the process of IDD for 50 consecutive subjects with single or recurrent episodes of low back pain, and concluded that the process of IDD could be detected by T1ρ values, particular at early stage. Borthakur et al[17] found that T1ρ was significantly lower in the painful discs from control and non-painful discs. T1ρ values might provide a reliable quantification of longitudinal biochemical changes of degeneration,[18] which would be beneficial for timely developing and appling new therapeutics.[4,19]

Injection of biocompatible hydrogel into degenerative discs has been studied for the treatment of IDD, and showed optimistic effects;[20] however, the optimal time window for the regenerative treatment of IDD is still unclear. Using T1ρ MR imaging, we found that there was a rapid degenerative stage in the early IDD process of rhesus monkeys, which had been demonstrated to be coincided with the rapid degeneration process of human lumbar intervertebral discs between Pfirrmann grades II and III.[21] We hypothesized that the rapid degenerative stage of IDD was the optimal time for hydrogel injection for treatment of IDD. In the present study, we used a rhesus monkey model of IDD and T1ρ MR imaging to determine the optimal timing of biocompatible hydrogel injection for the regenerative treatment of IDD.

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