Research progress and prospects of nanomaterials in imaging of central nervous system diseases

Abstract

Nanomaterials have garnered significant attention in recent years for their application in the imaging of central nervous system diseases (CNSDs). To comprehensively understand the research progress and trends in this field, this paper conducted a bibliometric analysis of relevant literature over the past fourteen years, systematically reviewing the research hotspots and development trends in the application of nanomaterials for CNSDs imaging. Using CiteSpace for visual data analysis, relationship networks among countries, institutions, journals, research categories, authors, and keywords were presented through specified mapping. The findings reveal that China is the country with the highest number of publications, the Chinese Academy of Sciences is the institution with the most published articles, and “Biomaterials” is the most frequently cited journal. Keywords such as fluorescence imaging, release, proteins, and targeted delivery represent current research hotspots, indicating a shift in focus toward precision imaging and intelligent delivery. Cluster analysis reveals that current research has progressed from single-performance optimization to the development of intelligent responsive nano-systems—integrating targeted delivery, environmentally responsive release, and multimodal imaging. However, nanomaterials still face multiple challenges and limitations spanning from basic research to clinical translation, and their application in CNSDs remains experimental. Therefore, further interdisciplinary research across materials science, chemistry, biology, and medicine is necessary to break down disciplinary barriers and promote clinical translation, ultimately enabling revolutionary breakthroughs in nano-theranostic technologies for central nervous system diseases.

Introduction

With the aging of the world population and the influence of viruses and other factors, the incidence rate of central nervous system diseases (CNSDs) is increasing, which seriously threatens human health and greatly reduces the quality of life for patients [1, 2]. However, there are many causes to induce CNSDs, how to differentiate and diagnose CNSDs is a difficult problem. The appearance of imaging technology enables CNSDs to be diagnosed quickly and accurately [3]. In imaging examination, contrast agents can be used to enhance image contrast, which is more conducive to the diagnosis and treatment guidance for CNSDs [4]. Therefore, it is very important to design targeted and efficient contrast agents for CNSDs imaging.

Nanomaterials, as a novel contrast agent, have been extensively utilized in CNSDs research due to their distinctive physical and chemical properties, including small size, large specific surface area, and high stability [5–7]. Once the safety concerns have been addressed, these nanomaterials are poised to illuminate clinical applications associated with the nervous system, exhibiting immense potential in the future. In CNSDs imaging diagnosis, nanomaterials can be used to monitor and identify changes in neurodegenerative diseases or central nervous system tumors [7, 8]. In addition, the combination of nanomaterials and therapeutic diagnostic agents can also be used for the treatment of CNSDs [9]. Therefore, nanomaterials as contrast agents in the future will break through the limitations of traditional contrast agents that can only function in diagnosis, providing a one-stop solution for diagnosing and treating diseases. Although various nanomaterials have been developed for imaging of CNSDs, few studies systematically summarize the application of nanomaterials in CNSDs imaging through bibliometric methods.

In this study, we collected relevant literatures of nanomaterials in CNSDs imaging from 2012 to 2025 in the Web of Science Core Collection (WoSCC). Based on the current bibliometrics methods, 1472 articles were visually analyzed through CiteSpace and the corresponding knowledge spectrum was made. We aimed to visualize the scientific achievements of nanomaterials in CNSDs imaging through knowledge maps, and explore the research hot spots of nanomaterials in CNSDs imaging.

Methods

Data collection and search strategy

The Science Citation Index-Expanded and Science Citation Index of WoSCC was selected as the data source. The following terms were used to collect scientific citations from 2012 to 2025:

TS= (nanoparticle* or nanomaterial* or nanodot* or “quantum dot*” or nanosphere* or nanorod* or nanofiber* or nanotube* or nanosheet* or nanocomposite* or nanodevice* or nanocluster* or nanotechn* or nanocarrier* or nanowire* or nanoliposome* or nanoemulsion* or nanocrystal* or nanogels* or nanoconjugate* or nanodiamond* or “metal organic framework” or MOF* or nanozymes or metallic nanomaterials).

And

TS= (“X-ray imaging” or CT or MRI or “magnetic resonance imaging” or “computed tomography” or “compute tomography” or “positron emission tomography” or “single-photon emission computed tomography” or “pet-ct” or “spect-ct” or “pet-mri” or “spect” or “SPECT/CT” or “PET/CT” or “ultrasound imaging” or ultrasonography or “fluorescence imaging” or “neuroimaging” or “Brain Imaging” or “Imaging, Brain” or “NIR imaging” or “photoacoustic imaging” or NIR imaging).

And

TS= (“multiple sclerosis” or “amyotrophic lateral sclerosis” or “Parkinson’s” or “Parkinson Disease” or “Alzheimer’s” or “Alzheimer’s disease” or “Huntington’s” or “Huntington disease” or neurodegenerative or “neurodegenerative disorder” or “neurodegenerative disease” or neurodegeneration or “Parkinson’s disease” or “Alzheimer disease” or “Huntington’s disease” or “brain tumor*” or “brain neoplasm*” or encephalitis or neuroinflammation or glioma or glioblastoma or “neurological disease*” or “neurological disorder” or “brain disorder” or “brain injury” or “central nervous system disease” or “CNS disease” or “central nervous system disorder” or “CNS disorder” or “clinical neurology” or neuroscience or epilepsy or stroke or hereditary ataxia or cerebrovascular).

The publications only include papers and reviews in English. Finally, 2030 publications were retrieved from WoSCC. We downloaded the raw data of the retrieved publications from WoSCC as plain text files, including full records and cited references. In addition, an independent examination was conducted by two radiologists (Zongqian Wu and Lihua Deng), excluding articles unrelated to the application of nanomaterials in CNSDs imaging, resulting in a final selection of 1472 articles. In cases of disagreement, a third experienced imaging specialist (Chen Liu) was consulted to determine whether to exclude the article. The whole research idea and flow chart are shown in Fig. 1.

Fig. 1.

Flow chart of this study, CNSDs: Central Nervous System Diseases. *Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). **If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools

Data analysis

The collected data were then systematically analyzed using OriginPro 8, Excel 2019 and CiteSpace (Version 6.4. R1). OriginPro 8 and Excel 2019 were used to describe the number trend of articles published each year and the distribution of article journals, while CiteSpace was used to build a knowledge network map of keywords/authors/institutions/countries. In addition, CiteSpace can also be used for co-citation analysis of literature/authors/journals and keyword burst detection. In this study, we set the time slice as one year and created different types of knowledge network maps. Finally, the content of each cluster is also analyzed using LLR weighting, according to Chen Chaomei’s suggestion [10].

Results

Analysis of annual publication

The total 1472 publications about nanomaterials in CNSDs imaging were obtained from WoSCC, including 1211 articles (82.27%) and 261 reviews (17.73%). The publications number trend published annually on nanomaterials in CNSDs imaging from 2012 to 2025 was exhibited in Fig. 2. The number of articles published in the first four years has increased from 50 in 2012 to 98 in 2015. Notably, the number of publications on nanomaterials for CNSDs imaging reached its highest point in 2025. The current research was still focused on the application of nanomaterials for CNSDs imaging. From the time distribution map of the literatures number, it can be found that the nanomaterials research in the field of CNSDs imaging has developed and received much attention in the past fourteen years. The phenomenon could be attributed to the emergence of imaging technology, which provided an ideal tool to study the imaging problems for CNSDs. In addition, the combination of therapy and imaging through integrated nanomaterials also provided a new idea for the treatment of CNSDs.

Fig. 2.

The number and citation frequency trend of annual publications about nanomaterials in the field of CNSDs imaging from 2012 to 2025

Analysis of journals and co-cited journals

As shown in Fig. 3A, a co-citation map of journals was generated by CiteSpace, and 58 journals met the minimum citation volume of 200. In Citespace, “N” represents the node, that is, the node where the journal appears. The larger the font size of the journal, the higher the frequency of the journal’s appearance in 1472 pieces of data. “E” represents the connection and the connection between nodes represents the connection between journals. The thicker the connection, the higher the frequency of appearance in the same article, which shows the cooperation between journals. There are 735 nodes and 6276 connecting positions in the atlas of cited journals. It can be seen intuitively from the figure that there are many and close connections between some journals, such as PNAS, Biomaterials etc. In addition, we can also conclude that the most frequently cited journal was Biomaterials (911), followed by ACS Nano (837) and PNAS (675). Among the top 10 journals, the highest IF for Advanced Materials is 26.80. From the top 10 journals of co-citation reference, it is found that 8 journals belonged to the category of “chemistry” or “materials”, and the other 2 journal was classified as “medicine”. From the analysis results, we can speculate that the application of nanomaterials in the CNSDs imaging field is more focused on the innovation of materials in chemistry, possibly driven by various factors including clinical safety concerns, the blood-brain barrier, targeting, and other related issues. Currently, most articles on nanomaterials in CNSDs have not been published in medical imaging journals, indicating that there are still many challenges in clinical conversion applications (Table 1).

Fig. 3.

A Journal co-citation analysis by CiteSpace; B Double map coverage of journals related to nanomaterials for CNSDs imaging

Table 1.

The top 10 journals in nanomaterials CNSDs imaging from 2012 to 2025

Ranking	Journal	Cited frequency	Centrality
1	Biomaterials	911	0.2
2	ACS Nano	837	0.08
3	PNAS	675	0.19
4	Journal of Controlled Release	643	0.09
5	Advanced Materials	624	0.04
6	Journal of the American Chemical Society	587	0.05
7	Small	565	0.1
8	Nanoscale	543	0.01
9	Angewandte Chemie International Edition	538	0.1
10	Scientific Reports	527	0.04

Moreover, a double map overlay map (Fig. 3B) of the journals was created to reflect the theme distribution of disciplines by selecting the JCR periodical map in the overlay map. Discipline association analysis is to study the composition of frontier and knowledge base by connecting the citing literatures with the disciplines of the cited literatures. The four colored wavy lines in the figure demonstrated the main citation paths. Through the co-citation analysis of the cited journals, we found that the applications of nanomaterials in CNSDs imaging mainly focused on biomedicine, molecular biology, toxicology, material science, chemistry and physics. This result can prove that nanomaterials combining with biology is participated in CNSDs imaging through relevant imaging methods.

Analysis of countries and institutes

In general, 66 countries/regions published 1472 publications on nanomaterials imaging research in CNSDs. The cooperation between countries/regions was shown in Fig. 4A. Table 2 provided details of the top 10 countries/regions and institutions. The number of publications ranked first in China (738), followed by the United States (371) and France (78), accounting for 80.64% of all publications. In addition, the three countries/regions with a large number of papers had also cooperated more closely with other countries/regions. In the national visualization map, China contributed 50.14% of the published articles. Regarding centrality, the United States ranked first with a value of 0.31, which indicated its central position in the field of CNSDs imaging with nanomaterials and its close relationship with other countries. It also showed that researchers in the United States tended to cooperate with other countries to complete research on nanomaterials in the field of CNSDs imaging.

Fig. 4.

A Map of countries/regions; B Map of institutions

Table 2.

Top 10 productive countries/regions and institutions related to nanomaterials in CNSDs imaging

Rank	Country/region	Counts (%)	Centrality	Institution	Counts (%)	Centrality
1	China	738 (50.14)	0.28	Chinese Acad Sci	131 (8.90)	0.69
2	USA	371 (25.20)	0.31	CNRS	58 (3.94)	0.22
3	France	78 (5.30)	0.22	Fudan Univ	56 (3.80)	0.07
4	India	70 (4.76)	0.14	Shanghai Jiao Tong Univ	47 (3.19)	0.11
5	Germany	67 (4.55)	0.16	Inserm	32 (2.17)	0.03
6	South Korea	58 (3.94)	0.00	Sun Yat Sen Univ	30 (2.04)	0.07
7	Canada	51 (3.46)	0.02	Univ California System	28 (1.90)	0.05
8	Spain	47 (3.19)	0.19	Univ Chinese Acad Sci	25 (1.70)	0.06
9	Italy	42 (2.85)	0.05	Capital Med Univ	24 (1.63)	0.06
10	Iran	40 (2.72)	0.05	Harvard Univ	24 (1.63)	0.08

A total of 189 institutions has studied the nanomaterials application in CNSDs imaging, and the map of cooperation network among institutions was shown in Fig. 4B. The size of nodes and fonts is proportional to the number of papers issued. The Chinese Academy of Sciences (131) issued the most papers, followed by Centre National de la Research Universities (58), Fudan University (56) and Shanghai Jiao Tong University (47). Comparatively speaking, six of the top 10 institutions were from China, which indicated Chinese institutions have more prominent research depth and breadth in the improvement of nanomaterials for CNSDs imaging in comparison with other countries. From the perspective of institutional contributions, the Chinese Academy of Sciences ranks first in terms of literature output and has the highest centrality, which indicates that the Chinese Academy of Sciences is an important bridge to promote inter agency cooperation, and has made great contributions in the field of nanomaterials for CNSDs imaging, thus promoting the nanomaterials development and progress for CNSDs imaging. According to the visualization analysis of countries/regions and institutions, China has not only made pioneering achievements in nanomaterials for CNSDs imaging but has also been actively engaged in international research collaborations.

Analysis of authors and co-cited authors

A total of 545 authors published papers and the collaboration between authors was showed in Fig. 5A. In addition, Table 3 listed the top 10 authors, among which Sheng, ZH (16 articles) was the author with the largest output of papers, followed by Zheng HR (15 articles), Hu, DH (14 articles) and Ye, N (14 articles). Furthermore, Author Co-citation Analysis (ACA) was conducted to reflect the relationship between co-cited authors. Through ACA analysis, the top 10 co-cited authors and their citations were determined (Table 3), and the relationship network between all cited authors was depicted (Fig. 5B). Liu Y (122) is cited the most times, followed by Zhang Y (109) and Wang Y (109). In the author visualization chart of literature retrieval, it is found that many authors explore the application of nanomaterials in CNSDs imaging, but most of them are independent individuals and the relationship between the authors is generally low. In addition, the top 10 most productive authors rarely appear on the list of the top 10 most co-cited authors. This indicates that high publication output does not necessarily equate to high citation impact, with the latter serving as a more effective indicator of an author’s academic influence. For co-cited authors, at least 33 co-cited authors have made significant contributions on nanomaterials in the field of CNSDs imaging. Although the research on nanomaterials in the field of CNSDs imaging has lasted for more than ten years, a stable and outstanding research group has not yet been formed. Therefore, it is necessary to focus on the nanomaterials for CNSDs imaging via tracking the academic frontier in real time in order to obtain more abundant and high-quality research results.

Fig. 5.

A Map of author relationship; B Map of co-cited author relationship

Table 3.

Top 10 authors, co-cited authors, and co-cited references in nanomaterials for CNSDs imaging

Rank	Author	Counts	Co-cited Author	Counts	Co-cited reference	Count
1	Sheng ZH	16	Liu Y	122	Tang W, 2019, CHEM SOC REV, V48, P2967	37
2	Zheng HR	15	Zhang Y	109	Arvanitis CD, 2020, NAT REV CANCER, V20	35
3	Hu DH	14	Wang Y	109	Hong GS, 2017, NAT BIOMED ENG, V1, P0	34
4	Ye L	14	Stupp R	103	Guo B, 2018, ADV MATER, V30, P0	27
5	Liu B	13	Weissleder R	103	Tan AC, 2020, CA-CANCER J CLIN, V70	27
6	Guo B	13	Li Y	98	Antaris AL, 2016, NAT MATER, V15, P235	24
7	Gu W	12	Wang J	88	Sheng ZH, 2018, ADV MATER, V30, P0	24
8	Qian J	11	Zhang L	88	Furtado D, 2018, ADV MATER, V30, P0	23
9	Lux Francois	10	Hong GS	87	Saraiva C, 2016, J CONTROL RELEASE, V235, P34	22
10	Shen J	10	Yang J	82	Jia YL, 2019, ACS NANO, V13, P386	21

Analysis of cited references

Table 3 also listed the first 10 co-cited references and the number of co-citations, in which Tang W (2019) ranked first in the number of citations [11]. This article highlights nanotechnology for brain cancer theranostics across the blood-brain barrier. It covers design strategies (size, shape, ligand modification) for enhanced delivery, various imaging techniques (MRI, PET, fluorescence, etc.), and therapeutic approaches (chemotherapy, gene therapy, PDT/PTT). Challenges like safety and clinical translation are also discussed. According to the Reference Co-citation Analysis (RCA), the keywords of the co-cited literatures were divided into 14 categories, and the keywords of clustering map shown in Fig. 6 were obtained. CiteSpace provided module value (Q value, Modularity Q) and average contour value (S value, Mean Silhouette) according to the network structure and the clarity of clustering. When Q value > 0.3, the clustering structure is significant, and when the S value reaches 0.5, it can be considered convincing. The Q value of Fig. 6 is  0.7496, and the S value is  0.6773, so the cluster structure of this map was very significant, and the results were convincing.

Fig. 6.

Map of co-cited reference

Besides that, we also used CiteSpace to explore the timeline of keyword clustering and the strong citation explosion of co-cited references. By combining the information from Figs. 6 and 7, we can conclude that the size and occurrence time of each category vary. We found that “#1 magnetic resonance imaging” and “#8 magnetic nanoparticles” were relatively early hotspots, while “#2 quantum dots,” “#3 NIR-II fluorescence,” and “#0 photothermal therapy” are currently popular research topics. The ascendancy of these latter topics reflects the field’s ongoing technological evolution. Near-infrared II imaging, for instance, leverages probes with minimal scattering and absorption to achieve deeper tissue penetration and superior signal-to-noise ratio for in vivo visualization [14, 15]. Quantum dots offer exceptional photostability and tunable emission spectra, enabling multiplexed labeling and longitudinal tracking of dynamic biological processes [16, 17]. On the therapeutic front, photothermal therapy converts light energy into localized heat for precise, minimally invasive ablation of pathological lesions [18, 19].

Fig. 7.

The time line view map of co-cited reference

From the timeline visualization of keyword co-citation clusters (Fig. 7), it is evident that research on nanomaterials in central nervous system diseases (CNSDs) imaging has undergone distinct phase-wise evolution. Prior to 2010, studies predominantly focused on well-established technologies such as magnetic resonance imaging (MRI) and magnetic nanoparticles, with the primary goal of applying them to the diagnosis and therapeutic evaluation of major diseases like brain tumors and Alzheimer’s disease, along with initial explorations of in vivo tracking for cell-based therapies (Clusters #1, #6, #8, #9, #10). The central question at this stage was whether nanomaterials could serve as effective tools for basic imaging and therapeutic intervention in the central nervous system. This period laid the essential technological foundation and application-oriented perspective for the field.

As research progressed, the period between 2010 and 2015 witnessed a notable paradigm shift, with optically mediated active intervention emerging as a new frontier. The combination of photoacoustic imaging and photothermal therapy marked a transition from passive diagnosis toward integrated diagnosis and therapy, while the focus on intraoperative imaging and stem cell tracking reflected a pursuit of precision in clinical translation (Clusters #0, #4, #12, #13). On the other hand, the blood-brain barrier became a focal point as a major delivery bottleneck, and research in this area, often coupled with physical-assisted delivery technologies such as focused ultrasound (Clusters #5, #7), aimed to establish efficient delivery channels for the aforementioned advanced diagnostic and therapeutic strategies. The research question has been elevated to how to design a multifunctional nano platform that can intelligently cross physiological barriers and achieve precise imaging and minimally invasive treatment simultaneously.

After 2015, the field entered a phase of deepening development, characterized by the pursuit of technological refinement and strategic optimization within the established paradigm. The evolution during this period is prominently reflected in two aspects. First, the refinement of imaging technologies, exemplified by quantum dots and NIR-II imaging (Clusters #2, #3), aimed to develop a new generation of optical probes with higher signal-to-noise ratios and deeper tissue penetration, seeking to surpass the physiological limitations of conventional imaging. Second, the advancement toward intelligent delivery strategies transformed delivery (Clusters #11) from a barrier to be overcome into a smart system requiring precise programming. Research emphasis shifted toward developing intelligent nanocarriers capable of responding to the lesion microenvironment and achieving spatiotemporally precise regulation. This evolutionary trajectory reveals that the field has progressed from early-stage technological application, through the innovation of active therapeutic paradigms, to the current phase of synergistic efforts aimed at overcoming both microscopic imaging limits and macroscopic delivery challenges.

Analysis of keywords co-occurrence and burst

The keyword co-occurrence map (Fig. 8A) showed the keywords whose co-occurrence frequency was greater than 80 times. In Fig. 8A, keywords with large fonts such as drug delivery and iron oxide nanoparticles appeared, which indicated that these keywords appeared frequently in 1472 articles. However, other keywords with relatively small sizes, such as toxicity and gold nanoparticles, also appeared in the figure, indicating that scholars still paid attention to other topics. In addition, Table 4 also listed the top 10 keywords in the literatures in the field after merging synonyms and excluding search words.

Fig. 8.

A Map of keywords co-occurrence; B Map of keywords clustering

Table 4.

Top 10 keywords

Ranking	Centrality	Counts	Keywords
1	0.06	372	Nanoparticles
2	0.08	266	Drug delivery
3	0.05	205	In vivo
4	0.06	204	Iron oxide nanoparticles
5	0.05	200	Delivery
6	0.05	173	Therapy
7	0.03	162	Magnetic resonance imaging
8	0.08	150	Blood brain barrier
9	0.03	133	Cancer
10	0.08	128	Alzheimers disease

In order to improve the accuracy of research fields, this paper used the keyword clustering function of CiteSpace to summarize the closely related keywords in Fig. 8A, and the obtained keyword clustering map was shown in Fig. 8B. In Fig. 8A, the closer the keyword is to the center, the more frequently it appears in the field. It can be seen from Fig. 8B that the current research focused on alzheimers disease, magnetic nanoparticles, photothermal therapy, molecular imaging and vascular permeability.

Through keyword cluster analysis (Fig. 8B), the current intellectual structure of this field is clearly centered around two major clinical focuses: brain tumors (#0) and Alzheimer’s disease (#3). This indicates that research has progressed from early-stage broad exploration to a deepened phase targeting the pathological characteristics of specific diseases. In the direction of brain tumors, research has formed a paradigm of “physically energy-mediated theranostics”, where the knowledge base closely integrates magnetic resonance imaging (#1), iron oxide nanoparticles (#6), photothermal therapy (#4), and focused ultrasound (#7) assisted delivery. This reflects a closed-loop clinical approach, where MRI localization is used to open blood-brain barrier channels via focused ultrasound, followed by imaging-guided photothermal ablation assisted by nanocarriers. In neurodegenerative diseases, a deep understanding of disease mechanisms is pursued, focusing on neuroinflammation (#2) and oxidative stress (#5), while actively exploring biomimetic delivery systems with higher biocompatibility, such as extracellular vesicles (#8). Notably, magnetic resonance imaging (#1) serves as a pivotal hub connecting these two major directions, highlighting its irreplaceable role as a core imaging and evaluation tool across diverse disease models. Meanwhile, delivery strategies exhibit a “disease-specific” specialization trend, with brain tumors favoring physically assisted potent delivery, whereas neurodegenerative disease research prefers biology-inspired intelligent delivery. This structured knowledge graph provides clear direction for designing next-generation nanotherapeutic platforms tailored to disease specificity.

Figure 9 showed the first 30 keywords that cited most explosively in the imaging research of the nanomaterials in CNSDs, which could reflect the latest research direction. We mainly focused on the keywords that will continue to burst until 2025, including “extracellular versicles” (strength 4.18), “release” (strength 6.42), “mechanisms” (strength 3.86), “hyperthermia” (strength 3.64), and “modulation” (strength 3.89), “targeted delivery” (strength 3.72) and “graphene quantum dots” ((strength 3.46).

Fig. 9.

Top 30 keywords with the strongest citation bursts

Through the analysis of the emergence of keywords, this study clearly reveals the dynamic evolution path of the forefront of research in this field (Fig. 9). In the early stage (2012–2017), the forefront focused on establishing animal models, verifying the feasibility of in vivo applications of basic materials, and exploring gene therapy and cell tracking around classic models such as malignant gliomas, which belonged to the technological foundation period. The forefront of mid-term (2018–2022) has significantly expanded, manifested in the diversification of treatment modalities (such as photodynamic therapy, the rise of radiotherapy) and the expansion of disease models (such as ischemic stroke). At the same time, in-depth research on biomimetic carriers such as extracellular vesicles and disease mechanisms marks a step towards therapeutic innovation and deepening biological understanding in the field. Recently (2022 present), the forefront is clearly pointing towards precision medicine and intelligent nanotechnology. The strong emergence of keywords such as targeted delivery, controllable release, and precise regulation, as well as the emergence of new functional materials such as graphene quantum dots, jointly outline the core direction of future development: to build a next-generation nanoplatform that can intelligently sense the microenvironment of lesions and achieve precise diagnosis and treatment interventions in time and space. This sudden evolution trajectory from “basic verification” to “diversified exploration”, and then to ‘precise intelligence’ is mutually confirmed with the clustering analysis results of this study, fully depicting the dynamic landscape of the field from infancy to maturity and continuously transforming into clinical core challenges.

Discussion

Research hotspots

With the help of bibliometrics, this study summarized the nanomaterials application in the imaging of CNSDs. Through co-citation references, keywords co-occurrence analysis and keywords burst (Figs. 6, 7 and 8), the current research focus on nanomaterials in the field of CNSDs imaging was determined. These cluster nodes can be divided into four major research directions: (1) Research on the nanomaterials themselves included the preparations, functions and properties of “iron oxide nanoparticles”, “gold nanoparticles”, “quantum dots”, “magnetic nanoparticles” and “graphene quantum dots”; (2) The application of nanomaterials in CNSDs imaging reflected in “blood brain barrier”, “Alzheimer’s disease”, “brain tumor”, “Parkinson disease” and other common diseases; (3) The imaging methods of nanomaterials in CNSDs imaging contained “photoacoustic imaging”, “MRI” and “near-infrared imaging”; (4) The integration of diagnosis and treatment using nanomaterials in CNSDs primarily includes “photothermal therapy”, “sonodynamic therapy”, and “photodynamic therapy”. Chronologically, recent research has primarily focused on “photoacoustic imaging” [12, 13], “near-infrared II imaging” [14, 15], “quantum dots [16, 17]”, “photothermal therapy” [18, 19], and “focused ultrasound” [20, 21]. This indicates that the current research direction has shifted from fundamental imaging and treatment toward a technology-oriented approach centered on multimodality, high precision, and the integration of diagnosis and therapy. The integrated development of these technologies has jointly promoted the continuous evolution of central nervous system diseases towards precision, intelligence, and minimally invasive diagnosis and treatment.

Beyond this descriptive landscape, deeper structural analysis reveals that these four directions are not isolated but are orchestrated by an underlying “material-disease-technology” tripartite framework. The first dimension pertains to the intergenerational evolution of material families. The developmental trajectory from early-stage magnetic nanoparticles (#8) and iron oxide nanoparticles (#6), to mid-stage quantum dots (#2) and gold nanoparticles, and further to the recently emerging graphene quantum dots (Fig. 9) clearly illustrates a paradigm shift from “single-function carriers” toward “multifunctional intelligent platforms”. This progression is fundamentally driven by the field’s sustained pursuit of biocompatibility, targeting efficiency, and theranostic integration, thereby laying the material groundwork for the subsequent dimensions. The second dimension involves the focused deepening of disease models. Cluster analysis distinctly identifies two core pathologies-brain tumors (#0) and Alzheimer’s disease (#3) a divergence that profoundly reflects the decisive influence of disease pathology on research paradigms. Brain tumor research emphasizes physical energy-mediated precision ablation (closely associated with #4 photothermal therapy and #7 focused ultrasound), driven by the focal nature of lesions requiring robust intervention. In contrast, Alzheimer’s disease research focuses on modulating the pathological microenvironment (closely linked to #2 neuroinflammation, #5 reactive oxygen species, and #8 extracellular vesicles), consistent with the diffuse nature of the disease that demands sustained and mild intervention. This disease-specific divergence suggests that future research should move beyond the pursuit of universal platforms and instead design nanoplatforms tailored to distinct pathological characteristics. The third dimension encompasses the convergent innovation of technological pathways. Burst keyword analysis (Fig. 9) indicates that research frontiers have evolved from early-stage technical validation-characterized by terms such as “in vivo” and “gene delivery” to current intelligent phases marked by “targeted delivery”, “controlled release”, and “precise modulation”. This transition signifies a paradigmatic shift from addressing “what can be achieved” to exploring “how to achieve it optimally”. Notably, magnetic resonance imaging (#1) serves as a pivotal hub connecting the two major disease directions (Fig. 8B). Its irreplaceable role stems from its comprehensive utility in anatomical localization, functional assessment, and therapeutic monitoring-suggesting that future multimodal imaging systems should retain MRI as a core framework rather than merely stacking multiple modalities. Together, these three dimensions form a coherent logical chain of “foundation-orientation-implementation”: material innovation provides instrumental support for disease-specific investigations, while technological convergence translates the potential of the former two dimensions into practical theranostic capabilities. It is this intrinsic mechanism of synergistic evolution that continuously drives the field forward from single-function applications toward more systematic and intelligent paradigms.

Moving from specific technological modalities to underlying scientific objectives, this evolutionary trend is further substantiated by the trajectory of burst keywords (Fig. 9). The current research focus has significantly shifted towards core areas such as drug delivery, controllable release, precise regulation, and mechanism research, marking that this field has surpassed the early pursuit of imaging performance and entered a deep integration stage led by “precision medicine” and “intelligent diagnosis and treatment”. Drug delivery and controlled release reflect the deepening focus of research on constructing responsive and targeted delivery systems. The rise of regulation and mechanism research indicates that this field is no longer limited to verification at the application level, but rather delves into the molecular mechanisms and regulatory laws of the interaction between nanomaterials and living systems, in order to achieve more accurate diagnosis and therapeutic interventions. These emerging hotspots collectively point to a clear trend, and future research will focus more on building “intelligent nano-systems” that not only achieve high-precision imaging, but also have the ability to intelligently perceive the disease microenvironment, release drugs on demand, and regulate physiological processes, promoting the dynamic, accurate, and systematic diagnosis and treatment of central nervous system diseases.

Current challenges and limitations of nanomaterials in imaging of CNDSs

This study summarizes the research progress of nanomaterials in the field of central nervous system disease imaging through bibliometric analysis, but there may still be some limitations in this study. Firstly, literature retrieval relies on specific databases and topic strategies, which may lead to retrieval bias or omission of certain related studies. Secondly, the literature included in the analysis is limited to English publications, which may serve as sufficient information for research progress in other languages. In addition, although bibliometric methods can reveal macro trends, they are still insufficient in terms of specific technical details and deep-rooted obstacles to clinical translation. Although nanomaterials have shown great potential in the field of central nervous system disease imaging, they still face multiple key challenges and limitations from basic research to clinical translation.

1. The biocompatibility and long-term toxicity of nanomaterials in diagnosis and treatment. The metabolic pathways of most nanomaterials that remain in the brain for a long time, such as quantum dots and metal nanoparticles, are not yet clear, which may lead to neuroinflammation or abnormal activation of glial cells. The potential impact of material degradation products on blood-brain barrier integrity and neuronal function has not been fully evaluated.

2. The targeting efficiency and selectivity of nanomaterials are insufficient. Despite targeted strategies such as antibody and peptide modification, the enrichment efficiency of nanomaterials in lesion areas of complex brain tissue is generally low, and these materials are easily absorbed non-specifically by normal cells.

3. Nanomaterials lack large-scale preparation and standardization. The current complex synthesis process results in significant inter batch differences, making it difficult to meet the uniformity and stability requirements of clinical grade materials.

4. Imaging technology has limited penetration depth. Optical imaging technology is still limited by skull scattering and tissue absorption, resulting in severe signal attenuation in deep brain regions.

5. The blood-brain barrier remains a bottleneck in the delivery system. Although focused ultrasound can temporarily open the blood-brain barrier, there is still insufficient standard control over the degree and time window of opening, which poses a risk of brain edema or damage to neurovascular units.

6. The synergistic mechanism in the integration of nanomaterial diagnosis and treatment is not yet clear. The combination of photothermal/photodynamic therapy and imaging functions is still mostly at the technical level, and systematic research on energy transfer efficiency, thermal diffusion boundary control, and their impact on neural circuit function is still needed.

7. The preparation cost of multifunctional nanoprobes is high, and brain drug delivery requires combined surgery or high-end influencing equipment guidance, further pushing up treatment costs.

Conclusions and perspectives

This study revealed the complete development trajectory of nanomaterials in the field of central nervous system disease imaging from infancy to foresight through a bibliometric analysis system: the early focus was on the validation stage of magnetic resonance imaging technology based on magnetic nanoparticles (before 2010); Subsequently, it entered a breakthrough period of integrated diagnosis and treatment paradigms such as photoacoustic imaging and photothermal therapy (2010–2015), accompanied by technologies such as focused ultrasound to overcome the bottleneck of blood-brain barrier delivery; Recently, it has moved towards the deep integration stage of imaging precision and intelligent delivery (after 2015). This evolutionary path clearly demonstrates the scientific development logic from “technological verification” to “paradigm innovation” and then to “system optimization”. The current research focus has shifted from single performance optimization to the construction of intelligent responsive nano-systems-integrating targeted delivery, environmental response release, and multimodal imaging functions, reflecting the clear direction of precision medicine and intelligent diagnosis and treatment. This evolutionary trajectory, as elucidated through the “material—disease—technology” tripartite framework, underscores the field’s coherent progression toward systematic and intelligent paradigms. However, clinical translation still faces enormous challenges, and most studies are still at the stage of experimental animal models and lack a standardized evaluation system for clinical grade materials.

Facing the future, this field urgently needs to build an interdisciplinary integrated innovation ecosystem: through deep collaboration between materials chemists, biomedical engineers, neuroscientists, and clinical physicians, establish a full chain transformation path from molecular design, animal validation to preclinical research. The key development directions should include: (1) developing multifunctional nanoprobes with clinical compatibility; (2) Developing precise and controllable delivery systems and barrier regulation technologies; (3) Build an intelligent diagnosis and treatment system that can provide real-time feedback on treatment response; (4) Establish a standardized biosafety and efficacy evaluation system. Only by breaking down disciplinary barriers and promoting bidirectional knowledge flow between laboratory and clinical settings can we ultimately achieve revolutionary breakthroughs in nano-diagnosis and treatment technology in the field of central nervous system diseases, providing truly accurate diagnosis and treatment solutions for major brain diseases such as Parkinson’s disease and Alzheimer’s disease.

Abbreviations

CNSDs

Central nervous system diseases

NIR

Near-infrared

PDT

Photodynamic therapy

PTT

Photothermal therapy

MRI

Magnetic resonance imaging

Author contributions

H.F.L. and L.H.D. wrote the main manuscript text and prepared figures, tables. Z.Q.W. and C.L. conducted a literature search and funding. All authors discussed the results and contributed to the final manuscript.

Funding

This study was supported by the National Natural Science Foundation of China (82071910, 81601478, and 82572201) and the Natural Science Foundation Project of Chongqing (CSTB2024NSCQ-MSX3439).

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

All authors have approved the content of the manuscript prior to its submission for publication.

Competing interests

The authors declare no competing interests.