Can diffusion tensor imaging unlock the secrets of the growth plate?

"How tall will I be?" Every paediatrician has been asked this during their career. The growth plate is the main site of longitudinal growth of the long bones. The chondrocytes in the growth plate have a columnar pattern detectable by diffusion tensor imaging (DTI). DTI shows the diffusion of water in a tissue and whether it is iso- or anisotropic. By detecting direction and magnitude of diffusion, DTI gives information about the microstructure of the tissue. DTI metrics include tract volume, length, and number, fractional anisotropy (FA), and mean diffusivity. DTI metrics, particularly tract volume, provide quantitative data regarding skeletal growth and, in conjunction with the fractional anisotropy, be used to determine whether a growth plate is normal. Tractography is a visual display of the diffusion, depicting its direction and amplitude. Tractography gives a more qualitative visualization of cellular orientation in a tissue and reflects the activity in the growth plate. These two components of DTI can be used to assess the growth plate without ionizing radiation or pain. Further refinements in DTI will improve prediction of post-imaging growth and growth plate closure, and assessment of the positive and negative effect of treatments like cis-retinoic acid and growth hormone administration.

Specialist learning curves and clinical feasibility of introducing a new MRI grading system for skeletal maturity.

Objective: MRI is an emerging imaging modality to assess skeletal maturity. This study aimed to chart the learning curves of paediatric radiologists when using an unfamiliar MRI grading system of skeletal maturity and to assess the clinical feasibility of implementing said system. Methods: 958 healthy paediatric volunteers were prospectively included in a dual-facility study. Each subject underwent a conventional MRI scan at 1.5 T. To perform the image reading, the participants were grouped into five subsets (subsets 1-5) of equal size (n∼192) in chronological order for scan acquisition. Two paediatric radiologists (R1-2) with different levels of MRI experience, both of whom were previously unfamiliar with the study's MRI grading system, independently evaluated the subsets to assess skeletal maturity in five different growth plate locations. Congruent cases at blinded reading established the consensus reading. For discrepant cases, the consensus reading was obtained through an unblinded reading by a third paediatric radiologist (R3), also unfamiliar with the MRI grading system. Further, R1 performed a second blinded image reading for all included subjects with a memory wash-out of 180 days. Weighted Cohen kappa was used to assess interreader reliability (R1 vs consensus; R2 vs consensus) at non-cumulative and cumulative time points, as well as interreader (R1 vs R2) and intrareader (R1 vs R1) reliability at non-cumulative time points. Results: Mean weighted Cohen kappa values for each pair of blinded readers compared to consensus reading (interreader reliability, R1-2 vs consensus) were ≥0.85, showing a strong to almost perfect interreader agreement at both non-cumulative and cumulative time points and in all growth plate locations. Weighted Cohen kappa values for interreader (R1 vs R2) and intrareader reliability (R1 vs R1) were ≥0.72 at non-cumulative time points, with values ≥0.82 at subset 5. Conclusions: Paediatric radiologists' clinical confidence when introduced to a new MRI grading system for skeletal maturity was high from the outset of their learning curve, despite the radiologists' varying levels of work experience with MRI assessment. The MRI grading system for skeletal maturity investigated in this study is a robust clinical method when used by paediatric radiologists and can be used in clinical practice. Advances in knowledge: Radiologists with fellowship training in paediatric radiology experienced no learning curve progress when introduced to a new MRI grading system for skeletal maturity and achieved desirable agreement from the first time point of the learning curve. The robustness of the investigated MRI grading system was not affected by the earlier different levels of MRI experience among the readers.

Elective one-minute full brain multi-contrast MRI versus brain CT in pediatric patients: a prospective feasibility study.

BACKGROUND: Brain CT can be used to evaluate pediatric patients with suspicion of cerebral pathology when anesthetic and MRI resources are scarce. This study aimed to assess if pediatric patients referred for an elective brain CT could endure a diagnostic fast brain MRI without general anesthesia using a one-minute multi-contrast EPI-based sequence (EPIMix) with comparable diagnostic performance. METHODS: Pediatric patients referred for an elective brain CT between March 2019 and March 2020 were prospectively included and underwent EPIMix without general anesthesia in addition to CT. Three readers (R1-3) independently evaluated EPIMix and CT images on two separate occasions. The two main study outcomes were the tolerance to undergo an EPIMix scan without general anesthesia and its performance to classify a scan as normal or abnormal. Secondary outcomes were assessment of disease category, incidental findings, diagnostic image quality, diagnostic confidence, and image artifacts. Further, a side-by-side evaluation of EPIMix and CT was performed. The signal-to-noise ratio (SNR) was calculated for EPIMix on T1-weighted, T2-weighted, and ADC images. Descriptive statistics, Fisher's exact test, and Chi-squared test were used to compare the two imaging modalities. RESULTS: EPIMix was well tolerated by all included patients (n = 15) aged 5-16 (mean 11, SD 3) years old. Thirteen cases on EPIMix and twelve cases on CT were classified as normal by all readers (R1-3), while two cases on EPIMix and three cases on CT were classified as abnormal by one reader (R1), (R1-3, p = 1.00). There was no evidence of a difference in diagnostic confidence, image quality, or the presence of motion artifacts between EPIMix and CT (R1-3, p ≥ 0.10). Side-by-side evaluation (R2 + R4 + R5) reviewed all scans as lacking significant pathological findings on EPIMix and CT images. CONCLUSIONS: Full brain MRI-based EPIMix sequence was well tolerated without general anesthesia with a diagnostic performance comparable to CT in elective pediatric patients. TRIAL REGISTRATION: This study was approved by the Swedish Ethical Review Authority (ethical approval number/ID Ethical approval 2017/2424-31/1). This study was a clinical trial study, with study protocol published at ClinicalTrials.gov with Trial registration number NCT03847051, date of registration 18/02/2019.

Diffusion tensor imaging of the physis: the ABC's.

The physis, or growth plate, is the primary structure responsible for longitudinal growth of the long bones. Diffusion tensor imaging (DTI) is a technique that depicts the anisotropic motion of water molecules, or diffusion. When diffusion is limited by cellular membranes, information on tissue microstructure can be acquired. Tractography, the visual display of the direction and magnitude of water diffusion, provides qualitative visualization of complex cellular architecture as well as quantitative diffusion metrics that appear to indirectly reflect physeal activity. In the growing bones, DTI depicts the columns of cartilage and new bone in the physeal-metaphyseal complex. In this "How I do It", we will highlight the value of DTI as a clinical tool by presenting DTI tractography of the physeal-metaphyseal complex of children and adolescents during normal growth, illustrating variation in qualitative and quantitative tractography metrics with age and skeletal location. In addition, we will present tractography from patients with physeal dysfunction caused by growth hormone deficiency and physeal injury due to trauma, chemotherapy, and radiation therapy. Furthermore, we will delineate our process, or "DTI pipeline," from image acquisition to data interpretation.

DTI assessment of the maturing growth plate of the knee in adolescents and young adults.

PURPOSE: To assess the growth plates of the knee in a healthy population of young adults and adolescents using DTI, and to correlate the findings with chronological age and skeletal maturation. METHODS: A prospective, cross-sectional study to assess the tibial and femoral growth plates with DTI in 155 healthy volunteers aged between 14.0 and 21 years old. Echo-planar DTI with 15 directions and b value of 0 and 600 s/mm2 was performed on a 3 T whole-body scanner. RESULTS: A relationship was observed between chronological age and most DTI metrics (fractional anisotropy, mean diffusivity, and radial diffusivity), tract length and volume. (No significant relationship could be seen for axonal diffusivity and tract length.) Subdivision according to skeletal maturation showed the greatest tract lengths and volumes seen in stage 4b and not 4a. The intra-observer agreement was significant (P = 0.01) for all the measured variables, but agreement varied (femur 0.53 - 0.98; tibia 0.58 - 0.98). Spearman's correlation showed a significant correlation for age (P = 0.05; P = 0.01) as well as for the fractional anisotropy value within all variables in both femur and tibia. Tract number and volume had a similar correlation with most variables, especially the DTI metrics, and would seem to be interchangeable. CONCLUSION: The current study indicates that DTI metrics could be a tool to assess the skeletal maturation process of the growth plate and its activity. Tractography seems promising to assess the activity of the growth plate in a younger population but must be used with caution in the more mature growth plate.

Magnetic resonance and diffusion tensor imaging of the adolescent rabbit growth plate of the knee.

PURPOSE: To assess the ability of MRI-DTI to evaluate growth plate morphology and activity compared with that of histomorphometry and micro-CT in rabbits. METHODS: The hind limbs of female rabbits aged 16, 20, and 24 wk (n = 4 per age group) were studied using a 9.4T MRI scanner with a multi-gradient echo 3D sequence and DTI in 14 directions (b-value = 984 s/mm2 ). After MRI, the right and left hind limb were processed for histological analysis and micro-CT, respectively. The Wilcoxon signed-rank test was used to evaluate the height and volume of the growth plate. Intraclass correlation and Pearson correlation coefficient were used to evaluate the association between DTI metrics and age. RESULTS: The growth plate height and volume were similar for all modalities at each time point and age. Age was correlated with all tractography and DTI metrics in both the femur and tibia. A correlation was also observed between all the metrics at both sites. Tract number and volume declined with age; however, tract length did not show any changes. The fractional anisotropy color map showed lateral diffusion centrally in the growth plate and perpendicular diffusion in the hypertrophic zone, as verified by histology and micro-CT. CONCLUSION: MRI-DTI may be useful for evaluating the growth plates.

A cross-sectional magnetic resonance imaging study of factors influencing growth plate closure in adolescents and young adults.

AIM: To assess growth plate fusion by magnetic resonance imaging (MRI) and evaluate the correlation with sex, age, pubertal development, physical activity and BMI. METHODS: Wrist, knee and ankle of 958 healthy subjects aged 14.0-21.5 years old were examined using MRI and graded by two radiologists. Correlations of growth plate fusion score with age, pubertal development, physical activity and BMI were assessed. RESULTS: Complete growth plate fusion occurred in 75%, 85%, 97%, 98%, 98% and 90%, 97%, 95%, 97%, 98% (radius, femur, proximal- and distal tibia and calcaneus) in 17-year-old females and 19-year-old males, respectively. Complete fusion occurs approximately 2 years earlier in girls than in boys. Pubertal development correlated with growth plate fusion score (ρ = 0.514-0.598 for the different growth plate sites) but regular physical activity did not. BMI also correlated with growth plate fusion (ρ = 0.186-0.384). Stratified logistic regression showed increased odds ratio (OR F: 2.65-8.71; M: 1.71-4.03) for growth plate fusion of obese or overweight subects versus normal-weight subjects. Inter-observer agreement was high (Κ = 0.87-0.94). CONCLUSION: Growth plate fusion can be assessed by MRI; occurs in an ascending order, from the foot to the wrist; and is significantly influenced by sex, pubertal development and BMI, but not by physical activity.

Comparison of reliability of magnetic resonance imaging using cartilage and T1-weighted sequences in the assessment of the closure of the growth plates at the knee.

BACKGROUND: Growth development is traditionally evaluated with plain radiographs of the hand and wrist to visualize bone structures using ionizing radiation. Meanwhile, MRI visualizes bone and cartilaginous tissue without radiation exposure. PURPOSE: To determine the state of growth plate closure of the knee in healthy adolescents and young adults and compare the reliability of staging using cartilage sequences and T1-weighted (T1W) sequence between pediatric and general radiologists. MATERIAL AND METHODS: A prospective, cross-sectional study of MRI of the knee with both cartilage and T1W sequences was performed in 395 male and female healthy subjects aged between 14.0 and 21.5 years old. The growth plate of the femur and the tibia were graded using a modified staging scale by two pediatric and two general radiologists. Femur and tibia were graded separately with both sequences. RESULTS: The intraclass correlation was overall excellent. The inter- and intra-observer agreement for pediatric radiologists on T1W was 82% (κ = 0.73) and 77% (κ = 0.65) for the femur and 90% (κ = 0.82) and 87% (κ = 0.75) for the tibia. The inter-observer agreement for general radiologists on T1W was 69% (κ = 0.56) for the femur and 56% (κ = 0.34) for the tibia. Cohen's kappa coefficient showed a higher inter- and intra-observer agreement for cartilage sequences than for T1W: 93% (κ = 0.86) and 89% (κ = 0.79) for the femur and 95% (κ = 0.90) and 91% (κ = 0.81) for the tibia. CONCLUSION: Cartilage sequences are more reliable than T1W sequence in the assessment of the growth plate in adolescents and young adults. Pediatric radiology experience is preferable.

Chronological Age Assessment in Young Individuals Using Bone Age Assessment Staging and Nonradiological Aspects: Machine Learning Multifactorial Approach.

BACKGROUND: Bone age assessment (BAA) is used in numerous pediatric clinical settings as well as in legal settings when entities need an estimate of chronological age (CA) when valid documents are lacking. The latter case presents itself as critical as the law is harsher for adults and granted rights along with imputability changes drastically if the individual is a minor. Traditional BAA methods have drawbacks such as exposure of minors to radiation, they do not consider factors that might affect the bone age, and they mostly focus on a single region. Given the critical scenarios in which BAA can affect the lives of young individuals, it is important to focus on the drawbacks of the traditional methods and investigate the potential of estimating CA through BAA. OBJECTIVE: This study aims to investigate CA estimation through BAA in young individuals aged 14-21 years with machine learning methods, addressing the drawbacks of research using magnetic resonance imaging (MRI), assessment of multiple regions of interest, and other factors that may affect the bone age. METHODS: MRI examinations of the radius, distal tibia, proximal tibia, distal femur, and calcaneus were performed on 465 men and 473 women (aged 14-21 years). Measures of weight and height were taken from the subjects, and a questionnaire was given for additional information (self-assessed Tanner Scale, physical activity level, parents' origin, and type of residence during upbringing). Two pediatric radiologists independently assessed the MRI images to evaluate their stage of bone development (blinded to age, gender, and each other). All the gathered information was used in training machine learning models for CA estimation and minor versus adult classification (threshold of 18 years). Different machine learning methods were investigated. RESULTS: The minor versus adult classification produced accuracies of 0.90 and 0.84 for male and female subjects, respectively, with high recalls for the classification of minors. The CA estimation for the 8 age groups (aged 14-21 years) achieved mean absolute errors of 0.95 years and 1.24 years for male and female subjects, respectively. However, for the latter, a lower error occurred only for the ages of 14 and 15 years. CONCLUSIONS: This study investigates CA estimation through BAA using machine learning methods in 2 ways: minor versus adult classification and CA estimation in 8 age groups (aged 14-21 years), while addressing the drawbacks in the research on BAA. The first achieved good results; however, for the second case, the BAA was not precise enough for the classification.

Management strategies for children with COVID-19: ESPR practical recommendations.

During the outbreak of the COVID-19 pandemic, guidelines have been issued by international, national and local authorities to address management and the need for preparedness. Children with COVID-19 differ from adults in that they are less often and less severely affected. Additional precautions required in the management of children address their increased radiosensitivity, need for accompanying carers, and methods for dealing with children in a mixed adult-paediatric institution. In this guidance document, our aim is to define a pragmatic strategy for imaging children with an emphasis on proven or suspected COVID-19 cases. Children suspected of COVID-19 should not be imaged routinely. Imaging should be performed only when expected to alter patient management, depending on symptoms, preexisting conditions and clinical evolution. In order to prevent disease transmission, it is important to manage the inpatient caseload effectively by triaging children and carers outside the hospital, re-scheduling nonurgent elective procedures and managing symptomatic children and carers as COVID-19 positive until proven otherwise. Within the imaging department one should consider conducting portable examinations with COVID-19 machines or arranging dedicated COVID-19 paediatric imaging sessions and performing routine nasopharyngeal swab testing before imaging under general anaesthesia. Finally, regular personal hygiene, appropriate usage of personal protective equipment, awareness of which procedures are considered aerosol generating and information on how to best disinfect imaging machinery after examinations should be highlighted to all staff members.

Imaging assessment of children presenting with suspected or known juvenile idiopathic arthritis: ESSR-ESPR points to consider.

Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatic disease. It represents a group of heterogenous inflammatory disorders with unknown origin and is a diagnosis of exclusion in which imaging plays an important role. JIA is defined as arthritis of one or more joints that begins before the age of 16 years, persists for more than 6 weeks and is of unknown aetiology and pathophysiology. The clinical goal is early suppression of inflammation to prevent irreversible joint damage which has shifted the emphasis from detecting established joint damage to proactively detecting inflammatory change. This drives the need for imaging techniques that are more sensitive than conventional radiography in the evaluation of inflammatory processes as well as early osteochondral change. Physical examination has limited reliability, even if performed by an experienced clinician, emphasising the importance of imaging to aid in clinical decision-making. On behalf of the European Society of Musculoskeletal Radiology (ESSR) arthritis subcommittee and the European Society of Paediatric Radiology (ESPR) musculoskeletal imaging taskforce, based on literature review and/or expert opinion, we discuss paediatric-specific imaging characteristics of the most commonly involved, in literature best documented and clinically important joints in JIA, namely the temporomandibular joints (TMJs), spine, sacroiliac (SI) joints, wrists, hips and knees, followed by a clinically applicable point to consider for each joint. We will also touch upon controversies in the current literature that remain to be resolved with ongoing research. KEY POINTS: • Juvenile idiopathic arthritis (JIA) is the most common chronic paediatric rheumatic disease and, in JIA imaging, is increasingly important to aid in clinical decision-making. • Conventional radiographs have a lower sensitivity and specificity for detection of disease activity and early destructive change, as compared to MRI or ultrasound. Nonetheless, radiography remains important, particularly in narrowing the differential diagnosis and evaluating growth disturbances. • Mainly in peripheral joints, ultrasound can be helpful for assessment of inflammation and guiding joint injections. In JIA, MRI is the most validated technique. MRI should be considered as the modality of choice to assess the axial skeleton or where the clinical presentation overlaps with JIA.

Comparative analysis of power, work and muscle activation during weight-stack and iso-inertial flywheel resistance exercise in young adults with cerebral palsy.

INTRODUCTION: The development of efficient resistance exercise protocols to counteract muscle dysfunction in cerebral palsy is warranted. Whether individuals with cerebral palsy are able to perform iso-inertial resistance (flywheel) exercise in a comparable manner to typically developed subjects has never been experimentally tested. DESIGN: A comparative, controlled study. SUBJECTS: Eight young ambulatory adults with cerebral palsy (mean age 19 years; Gross Motor Function Classification System (GMFCS) I-III) and 8 typically developed control subjects (mean age 21 years). METHODS: Subjects performed acute bouts on the weight-stack and flywheel leg-press device, respectively. Range of motion, electromyography, power, work and muscle thickness (ultrasound) data were collected. RESULTS: Subjects with cerebral palsy were able to produce a greater eccentric/concentric peak power ratio on the flywheel (p < 0.05 vs ratio in weight-stack), however absolute values were lower (p < 0.05 vs weight-stack). Typically developed subjects produced more power per mm of thigh muscle than the cerebral palsy group, independent of leg, device and action. DISCUSSION: Subjects with cerebral palsy could not elicit the eccentric overload seen in typically developed subjects. Furthermore, peak power production per mm muscle was markedly reduced in both legs in subjects with cerebral palsy. In conclusion, this comparative study of weight-stack and flywheel exercise does not support the implementation of the current iso-inertial protocol for young adults with cerebral palsy.

RaceRunning training improves stamina and promotes skeletal muscle hypertrophy in young individuals with cerebral palsy.

BACKGROUND: Individuals with cerebral palsy (CP) are less physically active, spend more time sedentary and have lower cardiorespiratory endurance as compared to typically developed individuals. RaceRunning enables high-intensity exercise in individuals with CP with limited or no walking ability, using a three-wheeled running bike with a saddle and a chest plate for support, but no pedals. Training adaptations using this type of exercise are unknown. METHODS: Fifteen adolescents/young adults (mean age 16, range 9-29, 7 females/8 males) with CP completed 12 weeks, two sessions/week, of RaceRunning training. Measurements of cardiorespiratory endurance (6-min RaceRunning test (6-MRT), average and maximum heart rate, rate of perceived exertion using the Borg scale (Borg-RPE)), skeletal muscle thickness (ultrasound) of the thigh (vastus lateralis and intermedius muscles) and lower leg (medial gastrocnemius muscle) and passive range of motion (pROM) of hip, knee and ankle were collected before and after the training period. RESULTS: Cardiorespiratory endurance increased on average 34% (6-MRT distance; pre 576 ± 320 m vs. post 723 ± 368 m, p < 0.001). Average and maximum heart rate and Borg-RPE during the 6-MRT did not differ pre vs. post training. Thickness of the medial gastrocnemius muscle increased 9% in response to training (p < 0.05) on the more-affected side. Passive hip flexion increased (p < 0.05) on the less-affected side and ankle dorsiflexion decreased (p < 0.05) on the more affected side after 12 weeks of RaceRunning training. CONCLUSIONS: These results support the efficacy of RaceRunning as a powerful and effective training modality in individuals with CP, promoting both cardiorespiratory and peripheral adaptations.

Age Assessment of Youth and Young Adults Using Magnetic Resonance Imaging of the Knee: A Deep Learning Approach.

BACKGROUND: Bone age assessment (BAA) is an important tool for diagnosis and in determining the time of treatment in a number of pediatric clinical scenarios, as well as in legal settings where it is used to estimate the chronological age of an individual where valid documents are lacking. Traditional methods for BAA suffer from drawbacks, such as exposing juveniles to radiation, intra- and interrater variability, and the time spent on the assessment. The employment of automated methods such as deep learning and the use of magnetic resonance imaging (MRI) can address these drawbacks and improve the assessment of age. OBJECTIVE: The aim of this paper is to propose an automated approach for age assessment of youth and young adults in the age range when the length growth ceases and growth zones are closed (14-21 years of age) by employing deep learning using MRI of the knee. METHODS: This study carried out MRI examinations of the knee of 402 volunteer subjects-221 males (55.0%) and 181 (45.0%) females-aged 14-21 years. The method comprised two convolutional neural network (CNN) models: the first one selected the most informative images of an MRI sequence, concerning age-assessment purposes; these were then used in the second module, which was responsible for the age estimation. Different CNN architectures were tested, both training from scratch and employing transfer learning. RESULTS: The CNN architecture that provided the best results was GoogLeNet pretrained on the ImageNet database. The proposed method was able to assess the age of male subjects in the range of 14-20.5 years, with a mean absolute error (MAE) of 0.793 years, and of female subjects in the range of 14-19.5 years, with an MAE of 0.988 years. Regarding the classification of minors-with the threshold of 18 years of age-an accuracy of 98.1% for male subjects and 95.0% for female subjects was achieved. CONCLUSIONS: The proposed method was able to assess the age of youth and young adults from 14 to 20.5 years of age for male subjects and 14 to 19.5 years of age for female subjects in a fully automated manner, without the use of ionizing radiation, addressing the drawbacks of traditional methods.

Bone age assessment with various machine learning techniques: A systematic literature review and meta-analysis.

BACKGROUND: The assessment of bone age and skeletal maturity and its comparison to chronological age is an important task in the medical environment for the diagnosis of pediatric endocrinology, orthodontics and orthopedic disorders, and legal environment in what concerns if an individual is a minor or not when there is a lack of documents. Being a time-consuming activity that can be prone to inter- and intra-rater variability, the use of methods which can automate it, like Machine Learning techniques, is of value. OBJECTIVE: The goal of this paper is to present the state of the art evidence, trends and gaps in the research related to bone age assessment studies that make use of Machine Learning techniques. METHOD: A systematic literature review was carried out, starting with the writing of the protocol, followed by searches on three databases: Pubmed, Scopus and Web of Science to identify the relevant evidence related to bone age assessment using Machine Learning techniques. One round of backward snowballing was performed to find additional studies. A quality assessment was performed on the selected studies to check for bias and low quality studies, which were removed. Data was extracted from the included studies to build summary tables. Lastly, a meta-analysis was performed on the performances of the selected studies. RESULTS: 26 studies constituted the final set of included studies. Most of them proposed automatic systems for bone age assessment and investigated methods for bone age assessment based on hand and wrist radiographs. The samples used in the studies were mostly comprehensive or bordered the age of 18, and the data origin was in most of cases from United States and West Europe. Few studies explored ethnic differences. CONCLUSIONS: There is a clear focus of the research on bone age assessment methods based on radiographs whilst other types of medical imaging without radiation exposure (e.g. magnetic resonance imaging) are not much explored in the literature. Also, socioeconomic and other aspects that could influence in bone age were not addressed in the literature. Finally, studies that make use of more than one region of interest for bone age assessment are scarce.

Preserved Collateral Blood Flow in the Endovascular M2CAO Model Allows for Clinically Relevant Profiling of Injury Progression in Acute Ischemic Stroke.

Interventional treatment regimens have increased the demand for accurate understanding of the progression of injury in acute ischemic stroke. However, conventional animal models severely inhibit collateral blood flow and mimic the malignant infarction profile not suitable for treatment. The aim of this study was to provide a clinically relevant profile of the emergence and course of ischemic injury in cases suitable for acute intervention, and was achieved by employing a M2 occlusion model (M2CAO) that more accurately simulates middle cerebral artery (MCA) occlusion in humans. Twenty-five Sprague-Dawley rats were subjected to Short (90 min), Intermediate (180 min) or Extended (600 min) transient M2CAO and examined longitudinally with interleaved diffusion-, T2- and arterial spin labeling perfusion-weighted magnetic resonance imaging before and after reperfusion. We identified a rapid emergence of cytotoxic edema within tissue regions undergoing infarction, progressing in several distinct phases in the form of subsequent moderation and then reversal at 230 min (p < 0.0001). We identified also the early emergence of vasogenic edema, which increased consistently before and after reperfusion (p < 0.0001). The perfusion of the penumbra correlated more strongly to the perfusion of adjacent tissue regions than did the perfusion of regions undergoing infarction (p = 0.0088). This was interpreted as an effect of preserved collateral blood flow during M2CAO. Accordingly, we observed only limited recruitment of penumbra regions to the infarction core. However, a gradual increase in infarction size was still occurring as late as 10 hours after M2CAO. Our results indicate that patients suffering MCA branch occlusion stand to benefit from interventional therapy for an extended time period after the emergence of ischemic injury.