{'fraction_non_alphanumeric': 0.0333494441759304, 'fraction_numerical': 0.011599806669888834, 'mean_word_length': 5.029626032054395, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 1, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Skull metastases detecting on arterial spin labeling perfusion

Abstract Rationale: Detection of skull metastases is as important as detection of brain metastases because early diagnosis of skull metastases is a crucial determinant of treatment. However, the skull can be a blind spot for assessing metastases on routine brain magnetic resonance imaging (MRI). To the best of our knowledge, the finding of skull metastases on arterial spin labeling (ASL) has not been reported. ASL is a specific MRI sequence for evaluating cerebral blood flow using magnetized endogenous inflow blood. This study uses ASL as a routine sequence of brain MRI protocol and describes 3 clinical cases of skull metastases identified by ASL. The study also highlights the clinical usefulness of ASL in detecting skull metastases. Patient concerns: Three patients with known malignancy underwent brain MRI to evaluate for brain metastases. Diagnoses: All of the skull metastases were conspicuously depicted on routine ASL images, and the lesions correlated well with other MRI sequences. Interventions: Three patients received palliative chemotherapy. Outcomes: Three patients are being followed up regularly at the outpatient department. Lessons: The routine use of ASL may help to detect lesions in blind spots, such as skull metastases, and to facilitate the evaluation of intracranial pathologies without the use of contrast materials in exceptional situations.


Introduction
The skull is a common site of metastases from systemic malignancies; hence, early diagnosis has an impact on clinical judgment and clinical management. [1] In clinical practice, computed tomography (CT) is commonly used for evaluating bony abnormality, though magnetic resonance imaging (MRI) is also used for screening and assessing bone lesions. [2] In cases of skull metastases, MRI provides additional information, such as type, location, multiplicity, and anatomical relationship to the brain and other intracranial structures. [2] Even though skull metastases are not rare, the diagnosis is often difficult because they have a wide range of clinical manifestations and radiologic work up is not always available in clinical practice. The detection of skull metastases is not also easy in patients without a known malignancy.
In the literature, there are many studies on skull metastases and their radiological findings. However, there is hardly any report on skull metastases in arterial spin labeling (ASL). ASL is a noninvasive MRI technique used to measure cerebral blood flow (CBF) by inducing the magnetization of inflowing blood. [3] Recently, ASL has been applied to various intracranial diseases including neurodegenerative disease, cerebrovascular disease and brain tumors. [3] This study presents 3 clinical cases of skull metastases identified on ASL, a routine sequence of brain MRI protocol used at the institution where the study was conducted. This study also provides a brief review of skull metastases and highlights the clinical usefulness of ASL in detecting these metastatic conditions.

Case report
This was purely an observational case study, and the patient's management and outcome were unaltered. Therefore, no ethical approval was required for this case report. Written informed consent was obtained from the patient for publication of this case report and accompanying images.

Case 1
A 62-year-old woman with breast cancer underwent brain MRI evaluation for brain metastases. Brain MRI was performed using a 3T system (Signa Architect; GE Healthcare, Milwaukee, WI) with routine use of synthetic MRI and a 48-channel head coil. ASL was included in the routine brain MRI sequences with the following scan parameters: TR, 4732 ms; TE, 10.3 ms; field of view (FOV), 23 cm; section thickness, 5mm; NEX, 1; and acquisition time, 1minutes 50 seconds. Pseudocontinuous ASL technique was used with labeling delay of 2seconds. The brain MRI revealed an enhancing intraaxial mass with perilesional edema in the right frontal lobe (arrowheads in Fig. 1A-C) with increased CBF on ASL (arrowhead in Fig. 1D), suggesting brain metastases. In addition, there were 3 enhancing foci in bilateral parietal bones on enhanced 3D T1-weighted image (TIWI), which were suggestive of bone metastases (arrows in Fig. 1C, H). Two of the 3 bone metastases showed bone marrow signal change on synthetic T1WI (Fig. 1B, G) and T2-weighted image (T2WI) (Fig. 1A, F). However, one enhancing lesion in the left parietal bone (white arrow in Fig. 1H) demonstrated no definite signal change on T1WI and T2WI. All of the 3 skull metastases demonstrated increased CBF on ASL (Fig. 1D, I). On 18F-fluorodeoxyglucose positron emission tomography CT (18F-FDG PET-CT), the corresponding skull lesions showed increased metabolic activity (Fig. 1E, J). These findings were correlated well with finding from ASL.

Case 2
A 79-year-old woman had metastatic serous papillary carcinoma of unknown origin in the neck. The patient underwent brain MRI to evaluate for brain metastases. Brain MRI was performed using the same machine as in case 1. There were no intraaxial or extraaxial metastases on brain MRI. However, there was a focus of increased CBF on ASL in the right side of the clivus (Fig. 2D). The corresponding area exhibited subtle bone marrow signal change on synthetic T2WI ( Fig. 2A), T1WI (Fig. 2B), and the lesion showed mild enhancement on contrast enhanced 3D T1WI (Fig. 2C). The lesion was considered as bone metastases. Unlike routine sequences including T1WI and T2WI, ASL clearly demonstrated bone metastases by increased CBF. On 18F-FDG PET-CT, there was no metabolic change in the corresponding area (not shown).

Case 3
A 70-year-old man with lung cancer underwent brain MRI to evaluate for brain metastases. Brain MRI was performed using a 3T system (Ingenia CX; Phillips, Amsterdam, the Netherlands) Figure 1. A 61-year-old female with breast cancer underwent brain MRI for evaluation of brain metastases. There was an enhancing intraaxial mass with perilesional edema in the right frontal lobe suggesting brain metastases (arrowheads in A-C). On ASL, the enhancing mass demonstrated increased CBF (arrowhead in D). In addition to the intraaxial mass, there were 3 enhancing foci in the bilateral parietal bones on enhanced 3D T1WIs, suggestive of bone metastases (arrows in C, H). Two of the 3 enhancing lesions showed subtle bone marrow signal change on T1WIs (arrowheads in B, G) and T2WIs (arrowheads in A, F). However, one enhancing lesion in the left parietal bone (white arrow in H) demonstrated no definite signal change on synthetic T1WI and T2WI (F, G). On ASL, the 3 enhancing bone metastases showed increased CBF (arrows in D, I), and the skull metastases could therefore be easily detected. On 18F-FDG PET-CT, the corresponding bone lesions showed increased metabolic activities (arrows in E, J). ASL = arterial spin labeling, CBF = cerebral blood flow, MRI = magnetic resonance imaging, T1WI = T1-weighted image, T2WI = T2-weighted image. with a 32-channel head coil. ASL was included in the routine brain MRI sequences with the following scan parameters: TR, 4035 ms; TE, 11 ms; FOV, 24 cm; section thickness, 5 mm; NEX, 1; and acquisition time, 3 minutes 38 seconds. Pseudocontinuous ASL technique was used with labeling delay of 1.8 seconds. There were no brain metastases on brain MRI. However, there was bone marrow signal change in the clivus and left occipital condyle on T2WI (Fig. 3A, F), T1WI (Fig. 3B, G), and heterogeneous enhancement on enhanced 3D T1WI (Fig. 3C, H), suggestive of bone metastases. The lesions showed increased CBF on ASL (Fig. 3D, I). On 18F-FDG PET-CT, there was increased metabolic activity in the corresponding areas (Fig. 3E, J).

Discussion
The skull is a common site of blood-borne metastases from various malignancies and the incidence of skull metastases is increasing. [1,2] Although most skull metastases are easily detected by the use of routine brain MRI, they are often underestimated because of their wide range of symptoms, unavailable radiological workup or insufficient information regarding a known malignancy. [2,4] Skull metastases can lead to a fatal clinical course, such as progressive cranial neuropathy and increased intracranial pressure. [4] Therefore, early and appropriate diagnosis is important to decide a treatment plan. CT is commonly considered as an initial imaging modality for evaluating bone lesions, and bone windows is a useful method to depict osteolytic lesions, such as skull metastases. However, CT does not clearly visualize margins of skull metastases and the presence of transdural extension by skull metastases. [2] CT also has an inherent limitation regarding spatial resolution and soft tissue contrast for assessing coexisting brain metastases.
In contrast to CT, MRI provides a high sensitivity for evaluating intracranial pathologies, including skull and brain metastases, because of the associated excellent soft tissue contrast. [5] MRI can also provide more information regarding the location, multiplicity, and anatomical relationship to adjacent structures of metastases. [2] It is well-known that skull metastases show a loss of normal hyperintense fatty marrow substituted by hypointensity on nonenhanced T1WI with a variable T2 signal intensity. Fat suppressed T1WI demonstrates variable enhance-ment after injection of contrast material. [4] MRI is also useful to detect a direct invasion to adjacent structures, such as dura, brain parenchyma, or cranial nerves. [2] Therefore, meticulous radiological assessment of all sequences of brain MRI is crucial for evaluating obscure skull metastases in patients with known malignancies.
Other methods for diagnosing skull metastases include radionuclide bone scan and 18F-FDG PET-CT. Radionuclide bone scan has great sensitivity in detecting skull metastases, but it is known to be insufficient for purely osteolytic metastases. [6] 18F-FDG PET-CT has comparable diagnostic accuracy of bone metastases to bone scan, and it becomes an important oncological imaging study. [6] However, skull metastases can be missed on 18F-FDG PET-CT because the FOV intentionally excludes the skull vault because of its glucose content. [6] In the current cases, ASL was used as a routine sequence for brain MRI protocol. The results show that skull metastases have a conspicuous delineation on ASL in all 3 clinical cases. ASL is an MRI sequence that detects CBF using inflow blood as an endogenous tracer. [3] Because ASL is a noninvasive technique that does not require exogenous contrast agent, it is clinically applied in various intracranial diseases, including neurodegenerative diseases, cerebrovascular diseases, vascular malformations, epilepsy, and brain tumors. [3] In previous studies on neoplasms, ASL has been applied to evaluate intraaxial tumors and to assess treatment response and has been employed in cases where gadolinium is contraindicated. [3] A review of the literature shows that little previous work has focused on the clinical application of ASL in evaluating skull metastases.
Because of the removal of scalp tissues and background noise by postprocessing of ASL data, the skull does not display specific color on the multisection CBF maps. [7] In the cases examined in this study, this technical background was helpful to detect skull metastases which showed increased CBF on ASL. In case 2, clival metastasis was detected only through ASL during initial radiological evaluation, and it corresponded to signal change in other sequences. These data suggest that the routine use of ASL may help detect skull metastases as well as brain metastases in patients with known malignancies. In addition, ASL also has an inherent advantage over other modalities because of noninvasive and repeatable sequences without gadolinium. Therefore, it can www.md-journal.com be readily performed in patients with renal insufficiency or history of contrast-mediated side effects. In the current cases, all of the skull metastases were conspicuously depicted on routine ASL images, and the lesions correlated well with other MRI sequences. The findings of this report suggest that the routine use of ASL may help to detect lesions in blind spots, such as skull metastases, and to facilitate the evaluation of intracranial pathologies without the use of contrast materials in exceptional situations.