Browsing by Author "Miller, Courtney"
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Item Contrast-enhanced micro-CT approaches for visualizing musculoskeletal development in neonatal mice(2023) Stalls, Javan; Miller, Courtney; Gonzales, Lauren; Lesciotto, Kate; Handler, Emma; Organ, Jason; Menegaz, Rachel A.Contrast-enhanced micro-CT approaches for visualizing musculoskeletal development in neonatal mice Javan A. Stalls, Courtney A. Miller, Jason M. Organ, Emma K. Handler, Lauren A. Gonzales, Kate M. Lesciotto, Rachel A. Menegaz Purpose: While there are many forms of radiological imaging that can be used to gather anatomical data from biological specimens, computed tomography (CT) imaging has been the gold standard for visualizing dense tissue, such as bone, with detailed resolution. However, this imaging modality is not well suited for soft tissues (muscle, brain, abdominal organs, cartilage, etc.) due to their decreased tissue density. The inability to distinguish between soft tissues in CT scans limits our ability to investigate the bone-muscle interactions known to stimulate and direct bone modeling during early postnatal development. The development of contrast-enhancing staining agents, capable of binding materials to increase their radiodensity, has allowed for more accurate and enhanced visualizations of less dense soft tissues, such as muscle and brain structures. Contrast agents such as iodine have differential affinities for the different soft tissues in the body allowing for easier visualization and segmentation of soft tissues in relation to the skeleton. Previous studies have used contrast-enhanced CT (CE-CT) scanning to analyze early development of mice from prenatal stages to postnatal day 7. However, additional CE-CT imaging during the first three postnatal weeks is needed to understand muscle-bone interactions during critical periods of behavioral development, such as suckling and weaning. The goal of this project is to develop a CE-CT protocol and corresponding anatomical atlas showing the development of skeletal and soft tissue structures in the crania of neonatal mice from birth to weaning. Methods: Neonatal and preweaning mice (B6C3Fe a/a-Col1a2OIM/J) were euthanized on day of birth (P0), postnatal day 7 (P7), and postnatal day 14 (P14). Ethanol-fixed tissues were submerged in 1.25% iodine in 70% ethanol (I2E) for 2-14 days, with the skin intact in order to preserve cutaneous musculature. Both pre-stained and post-stained tissues were scanned using a MRS CT-80 micro-CT machine (20 µm3 voxel resolution). Results: Preliminary CE-CT scans following 10 days in an iodine stain present improved visualization of soft tissue (brain structures, cranial muscles, salivary glands) when compared to the baseline bone CT scans. Conclusion: These scans will be used to develop 3D models of musculoskeletal ontogeny from birth-weaning, providing insights into this critical developmental period. The use of CT contrast agents such as iodine offers new opportunities to investigate the anatomical interactions of bone and muscle during early development, and can be applied to investigate models of both normal growth and pathological disorders affecting musculoskeletal growth.Item Cranial Bone Ossification Trajectories in a Mouse Model of Osteogenesis Imperfecta(2023) Miller, Courtney; Lugo, Laura; Husain, Tooba S.; Organ, Jason; Handler, Emma; Gonzales, Lauren; Menegaz, Rachel A.Purpose: Osteogenesis imperfecta (OI) is a genetic disorder that affects the production of type I collagen. Altered collagen production results in delayed or impaired skeletal formation and biomineralization. It also results in the defining characteristics of OI: brittle bones and high rates of fractures. Investigations of skeletal growth in OI have primarily focused on the postcranial skeleton, where interrupted, atypical, and disorganized ossification is seen at long bone growth plates. However, few studies have investigated changes in craniofacial growth in OI and there are currently few early interventions to improve growth trajectories in this region. The current medication prescribed for children with OI to improve skeletal growth, such as bisphosphonates, have major side effects and are not suitable for long-term use. A better understanding of craniofacial development in OI can help with targeting specific developmental stages when new treatments can be administered to provide the best results. The aim of this study is to examine cranial ossification from birth to weaning to determine where and when differences in growth occur in OI. We hypothesize that starting at birth mice with OI will have delayed craniofacial growth due to the poor collagen formation. Methods: To test our hypothesis, we collected cranial bone volumes from micro-CT scans of the homozygous recessive OI murine model (OIM or B6C3Fe a/a-Col1a2oim/oim) and compared them to their wild type (WT) littermates. The OIM model has a COL1A2 mutation that has been found to express a similar skeletal phenotype to the severe form (type III) of OI in humans. Bone volumes were collected from birth (P0) and weaning (P21) from the nasal, frontal, parietal, interparietal, and occipital bones (n=2/genotype/timepoint). Results: At birth, OIM and WT bone volumes were similar. By weaning, bone volume was lower in OIM mice compared to WT mice. Our results demonstrate that OIM mice have reduced rates of bone ossification between birth and weaning, and these differences are most profound in the facial and occipital regions. Additionally, OIM skulls are characterized by low bone volume and potential delays in the closure of cranial sutures and fontanelles. Conclusions: This study suggests that the divergence in cranial ossification rates related to COL1A2 mutations occurs postnatally. Interventions to recover craniofacial bone growth in this experimental model should focus on the critical growth period between birth and weaning. Results from this research have the potential to assist in developing treatments and highlight the importance of early life development of the craniofacial bones in human patients with OI.Item Craniofacial Bone Mineral Density During Growth in Mice with Osteogenesis Imperfecta (OI)(2021) Miller, Courtney; Wright, Tommy; McBride, Alexandra H.; Organ, Jason; Menegaz, Rachel A.Purpose: Osteogenesis imperfecta(OI) is a genetic connective tissue defect resulting in fragile bones due to mutations affecting formation of type I collagen. Low bone mineral density (BMD) in the post-cranial skeleton has been reported in human patients and murine models with OI, yet little is known about craniofacial biomineralization in the disorder. Typically, skeletal mineralization is responsive to the strain environment. The aim of this study is to investigate longitudinal changes in craniofacial BMD in a mouse model of OI type III (most severe form), and to quantify BMD in regions relative to feeding biomechanical forces. Methods: Homozygous recessive OI murine (OIM), a mouse strain with a COL1A2 mutation modeling OI type III, and unaffected wild-type (WT) littermates were micro-CT scanned at weeks 4, 10, and 16. BMD in eight regions was analyzed using Bruker CTAnalyzer software and Mann-Whitney U tests. Results: OIM mice had significantly (p< 0.05) lower BMD than WT mice in all eight regions during week 4, no significant differences in week 10, and significant differences at the parietal bone, mandibular symphysis, and maxillary incisor regions during week 16. Absolute BMD was higher within regions proximal to the bite point at skeletal maturity. Conclusions: These results support a trend that OIM mice have lower BMD in the craniofacial skeleton compared to WT mice throughout growth and BDM in all mice is affected by proximity to bite forces. Understanding craniofacial mineralization patterns in OI could assist in the implementation of pharmaceutical interventions to increase BMD.Item Effects of Osteopathic Manipulative Treatment on Breastfeeding LATCH Assessments in Infants(2024-03-21) Morse, Katelyn; Murray, Cameron; Miller, Courtney; Griner, Stacey; Hensel, KendiImportance: Effective suckling is crucial for infants to gain nutrition, grow, and bond with their mothers. Suckling difficulties within the first month can put infants at a higher risk of early weaning. Successful suckling involves coordinated movements of the lips, tongue, and jaw which rely on input from cranial nerves. Half of mothers who stop breastfeeding in the first month report biomechanical issues, highlighting the need to address these challenges for successful breastfeeding. Osteopathic Manipulative Treatments (OMT) have been utilized to treat the infant population for a variety of somatic dysfunctions and may be effective for suckling difficulties. Objective: To evaluate infants’ LATCH assessment scores before and after OMT sessions in the term infant population with feeding difficulties. Design, Settings, and Participants: This was a longitudinal prospective study conducted between October 2022 and July 2023 of 40 term infants <6 months of age with at least one of the following conditions: feeding difficulty, ankyloglossia (tongue tie), difficulty gaining and/or maintaining weight. After completing an initial eligibility screening, patients and their parents attended two clinic visits one week apart. Parents completed a LATCH questionnaire to evaluate infant latching at the beginning of each visit (visits 1-2). A phone follow up was conducted two weeks after the second visit to collect the LATCH survey over the phone (visit 3). Interventions: Participants received two full body OMT treatments one week apart, done by two different osteopathic physicians. Main Outcomes and Measures: LATCH assessment tool assigns a score of 0, 1, or 2 for five components (Latch, Audible swallowing, Type of nipple, Comfort, Hold) of feeding for a possible total score of 10 points, with higher scores indicating better outcomes. LATCH numerical scores were compared between the two visits to gauge improvement of the infant’s feeding abilities following OMT. LATCH scores were compared between the first and second visit, the second and third visit, and from visit 1 to visit 3 using independent samples t-tests. Results: Infants in the study were an average of 7.1 weeks old (standard deviation (SD)=4.4), an average weight of 3.6kg (SD=0.4) and an average length of 20.4 inches (SD=0.9). The majority were of white ethnicity (80%), possessed medical insurance coverage (92%), and had insurance covering lactation consultants (61%). Statistical analyses revealed a significant improvement in the LATCH scores between Visit 1 (8.01) and 2 (8.47; p=0.012); a significant improvement in LATCH scores between Visit 2 (8.47) and Visit 3 (9.11; p=.005); and an overall significant improvement from Visit 1 to Visit 3 (p<.001). The improvement at Visit 2 compared to Visit 1 was significantly larger among those who were bottle-fed (change=1.35) compared to those who were breastfed (change=0.21; p=.004). Conclusions and Relevance: In term infant populations with feeding difficulties, OMT significantly improved the LATCH scores over the course of the study. There are specific subpopulations, such as infants who were bottle-fed, who may have greater improvement in LATCH scores following OMT. OMT remains strongly recommended in this patient population to help with difficulties pertaining to latching.Item Infant Somatic Dysfunction and Breastfeeding LATCH Assessments following Osteopathic Manipulative Treatment(2024-03-21) Murray, Cameron; Morse, Katelyn; Roop, Jay P.; Miller, Courtney; Griner, Stacey; Hensel, KendiPurpose Importance: Breastmilk is known to be beneficial for newborns but challenges with latching can provide a significant barrier for breastfeeding. Such challenges may possibly stem from biomechanical and neurological restrictions inhibiting proper latching and sucking in infants. Osteopathic Manipulative Treatment (OMT) may address somatic dysfunctions associated with these restrictions and improve breastfeeding outcomes. Objective: To evaluate changes in infant somatic dysfunctions after a single OMT treatment and assess correlation with changes in latching using the LATCH assessment tool. Methods OMT was performed on 40 participants seen at the For Babies’ Sake clinic in Fort Worth, Texas between October 2022-July 2023. Eligible patients under 6 months old met at least one of the following criteria: feeding difficulty, ankyloglossia, or difficulty maintaining weight. Exclusion criteria included neurologic conditions, cleft lip or palate, lingual frenectomy within 72 hours of visit, hospital admission, and any conditions in which OMT would be contraindicated. Intervention: During two visits 1 week apart, an Osteopathic physician assessed participants’ somatic dysfunctions in the following regions: OA/condyles, occiput and OM, frontal bones, nasion, maxilla/premaxilla, zygomas/TMJ/temporals, tongue/pterygoids, anterior cervical muscles/hyoid, trunk/viscera, ribs/mediastinum, sacrum, pelvis, hips, knees, and navicular regions. Somatic dysfunctions were rated as 0=no somatic dysfunction, 1=mild, 2=moderate, 3=severe, marked or resistant. Somatic dysfunctions were addressed with treatments including: myofascial release, balanced ligamentous tension, balanced membranous tension, osteopathic cranial manipulative medicine, or vibratory treatment by percussion hammer. Parents completed a standardized LATCH assessment during visits 1 and 2, and responded to a LATCH questionnaire after visit 2. The LATCH questionnaire was shown to be a validated measure of latch, audible swallowing, nipple type, comfort, and hold and results in scores of 0-10, with higher scores indicating better breastfeeding outcomes. Main Outcomes and Measures: Rated somatic dysfunctions were compared between visit 1 and 2 to assess for statistically significant improvement. Changes in somatic dysfunction and LATCH scores were also assessed for correlation using t-tests. Results Mean age was 7.14 weeks (standard deviation=4.44). The following regions showed significant reduction in somatic dysfunction (p<.05) from visits 1 to 2, with mean change values shown here: OA/Condyles: -.75, Tongue/Pterygoids: -0.58, Trunk/viscera: -0.50, and Navicular: -0.38. The mean sum of all somatic dysfunctions was also significantly reduced by 4.15 between visit 1 and 2 (p<.01). The sacrum region was related to LATCH score change, with lower sacrum improvement across visits negatively correlated to more improvement LATCH scores from visits 1-3 (p<.01) and visits 2-3 (p<.05). Conclusions These results suggest that a single osteopathic treatment may reduce somatic dysfunction in newborns in multiple body regions. The connection of somatic dysfunctions and LATCH scores needs further research. Though helpful for assessing latch quality, the LATCH assessment does not assess actual infant milk intake or weight gain. Future studies could compare weight gain between OMT treated infants and a control group. It would also be beneficial to replicate this study with additional Osteopathic physicians to determine if improved somatic dysfunction results are repeatable between physicians.Item Masticatory muscle morphology in early postnatal mice with osteogenesis imperfecta(2024-03-21) Ansari, Zahra; Miller, Courtney; Emmanuel, Tanusha; Handler, Emma; Gonzales, Lauren; Organ, Jason; Menegaz, Rachel A.Purpose: Osteogenesis imperfecta (OI) is a connective tissue disorder resulting from mutations in COL1A1 or COL1A2, responsible for encoding type I collagen alpha chains. While OI is primarily distinguished by manifestations of bone fragility, including recurrent fractures and bone deformities, muscle abnormalities have also been documented in those affected by OI. While prior research has shown postcranial muscle weakness in mouse models of OI, it remains unclear whether this also applies to feeding musculature and if these differences are present at birth or develop postnatally. This study investigates the development of the masticatory muscles during the early postnatal period in a mouse model. Our hypothesis posits that mice affected by OI will exhibit decreased muscle mass, and therefore potentially weaker muscles, in comparison to unaffected mice. Methods: Cranial tissues from OIM mice (B6C3Fe a/a-Col1a2oim/J) and unaffected wild type (WT) littermates were collected at day of birth (P0) and postnatal day 14 (P14). Tissues were fixed and stained with 1.25% buffered Lugol’s solution, then micro-CT scanned with a reconstruction of 0.02 mm3 voxels. 3D Slicer software was used to isolate and measure the volumes of the superficial masseter, deep masseter, and temporalis muscles. Muscle volumes were compared between genotypes using a Mann-Whitney U test. Results: At birth, no significant differences were observed in body mass or muscle volumes between OIM and WT mice. A trend was observed for OIM mice to have lower superficial masseter volumes compared to WT mice at P0, but this difference was not significant. At P14, OIM mice have significantly lower body weights (p=0.002). Data collection is ongoing for volumetric muscle data from the P14 stage. After birth, body masses diverge rapidly between OIM and WT mice. These growth curves suggest poor feeding performance during the suckling stage in OIM mice. Although masticatory muscle volumes (similar to body mass) start out similar between genotypes at birth, a trend for decreased superficial masseter volume in OIM mice suggests feeding musculature will also lag behind unaffected mice during early postnatal growth. Conclusion: The production of strain above an osteogenic threshold by feeding musculature is critical to typical craniofacial growth during early life. Weaker masticatory muscles may produce lower (yet still osteogenic) levels of strain, contributing to the midfacial hypoplasia seen in OIM mice. A better understanding of muscle development during this critical growth period will provide insight on feeding disorders seen in OI, and the development of the craniofacial phenotype in pediatric patients with OI.Item Microstructure & Macrostructure Interrelationship in the Growing Hard Palate(2022) Miller, Courtney; Steele, Ashley T.; Organ, Jason; Menegaz, Rachel A.Bone strength is the result of microstructure (bone material properties) and macrostructure (bone size and shape), and deficiencies in either can produce skeletal fragilities with an increased likelihood of injury. The micro- and macro-architecture work together during re/modeling, ensuring that the skeleton is resistant to repetitive loading and preventing fracture. Bone is particularly responsive to loading during the rapid growth occurring in early life. Within the craniofacial complex, the hard palate is a unique structure that undergoes continuous loading due to continuous resting/active tongue pressure and bite forces. Because of this, palatal growth is theorized to drive midfacial growth. The aim of this study is to investigate longitudinal changes in the palate when the relationship between microstructure and macrostructure is perturbed. Here we use the OIM mouse (B6C3FE a/a-Col1a2OIM/J), a strain with a mutation to the structural protein type I collagen, resulting in increased bone fragility and improper biomineralization. We hypothesize that OIM and unaffected wild-type (WT) mice will be most similar in bone micro- and macro-structure in regions of the palate that experience high loading and therefore high rates of bone modeling/remodeling. Mice were micro-CT scanned at two timepoints: week 4 (juvenile) and week 16 (adult). BMD was collected at 3 regions (anterior, mid, and posterior palate). Mann-Whitney U tests were used to compare BMD between genotypes. 28 fixed and 10 sliding landmarks were placed across the palate. Geometric morphologic analyses were conducted to determine variation between genotypes in overall shape and curvature throughout growth. Average BMD decreased along an anteroposterior gradient for all mice. While juvenile OIM mice had lower palate BMD than WT mice at all regions, adult OIM mice had significantly lower BMD at only the anterior and posterior regions but not the midpalate. Procrustes ANOVA revealed significant differences in palatal shape between the genotypes at both the juvenile (p=0.001) and adult (p=0.0015) stages. Principal component analyses revealed that juvenile OIM mice had a shorter anterior palate and broader palate compared to WT mice, while adult OIM mice had a shorter posterior palate than WT mice. OI mice had flatter palatal arches in the coronal plane as juveniles, and in the midsagittal plane as juveniles and adults. Results show significant differences in palatal BMD and morphology between genotypes throughout growth, with fewer significant differences at the adult stage. Increased loading of the anterior palate during incisive gnawing may result in the convergence of bone macrostructure among adult mice, while increased strain at the midpalatal suture may necessitate increased BMD even in the presence of a biomineralization defect. Further research is needed to understand the functional significance of the anteroposterior palatal gradient and its relation to soft tissue attachments, particularly given the difference in oral behaviors between juveniles and adults.Item Neurocranial Growth in the OIM Mouse Model of Osteogenesis Imperfecta(2022) Husain, Tooba S.; Miller, Courtney; Steele, Ashley T.; Gonzales, Lauren; Handler, Emma; Organ, Jason; Menegaz, Rachel A.Osteogenesis imperfecta (OI) is a disorder of type I collagen characterized by abnormal bone formation and weakened bone architecture. Human patients with OI have larger cranial vaults (macrocephaly), altered cranial base morphology including basilar invagination and platybasia (skull base flattening), and midfacial underdevelopment. The neurocranial changes may affect both underlying nervous tissue and growth patterns of the facial skeleton. However, we still do not fully understand how and when these divergent morphologies occur. The aims of this study are: (1) to investigate the integrated development of the skull and the brain in amouse model of OI; and (2) to identify the developmental trajectories of these structures to facilitate future therapeutic interventions. We hypothesize that compared to unaffected mice, mice with OI will have decreased brain volumes due to an overall reduction in cranial size and decreased cranial base angles (CBA) due to platybasia. To test these hypotheses, we used the osteogenesis imperfecta murine (OIM or B6C3FE a/a-Col1a2/J), a model for the severe type III OI in humans, and unaffected wild-type (WT) littermates. Mice were imaged using in vivo micro-computed tomography (micro-CT) at the juvenile (week 4; 10 OIM/14 WT) and adult (week 16; 9OIM/11 WT) stages. All measurements were taken in 3D Slicer software. 82 cranial landmarks were used to calculate centroid size, an estimate of overall head size. The segmentations tool was used to create virtual endocasts as a proxy for brain volume. The angle tool was used to measure CBA in the midsagittal plane using threelandmarks: foramen cecum, midsphenoidal synchondrosis, and basion. Mann-Whitney U tests were used to compare centroid sizes, brain volumes, and CBA between the genotypes. Both juvenile (p=0.008) and adult (p=0.003) OIM mice were found to have absolutely smaller brains than WT mice. However, OIM mice also have significantly smaller cranial centroid sizes compared to WT mice (p=0.003, p< 0.001). When scaled to cranial size, juvenile mice had relatively larger brain volumes (p=0.016) butadult OIM relative brain volumes were not significantly different from WT. No significant difference was seen in CBA at the juvenile (p=0.065) or adult (p=0.171) stages, however a trend was observed for decreased CBA at the adult stage. These results suggest that neurocranial dysmorphologies in OI may be more severe at earlier stages of postnatal development. Previous analyses of these mice have documented relative skeletal macrocephaly in both juvenile and adults, however here we document an increase in relative endocranial volume only at the juvenile stage. A reduction in CBA during growth, possibly due to platybasia, may underlie this decoupling between external and internal cranial morphology. Future work will investigate the effect of CBA on facial growth and midfacial underdevelopment in these mice. A better understanding of the integration and growth trajectory of the neurocranium is foundational for formulating treatments to manage basicranial instabilities in patients with OI. Support or Funding Information Funding was provided by an Indiana University Collaborative Research Grant, Ralph W. and Grace Showalter Trust, and a UNTHSC Physiology & Anatomy SEED Grant.Item Osteogenesis Imperfecta: Implications of Using Micro-CT for Visualizing Developmental Variation in the Middle and Inner Ear of OIM Mice(2023) Judd, Dallin; Stucki, Brenton; Miller, Courtney; Handler, Emma; Menegaz, Rachel A.; Gonzales, LaurenOsteogenesis Imperfecta: Implications of Using Micro-CT for Visualizing Developmental Variation in the Middle and Inner Ear of OIM Mice Dallin R. Judd1, Brenton R. Stucki1, Courtney A. Miller2, Emma Handler3, Rachel A. Menegaz2, Lauren A. Gonzales2 1 Texas College of Osteopathic Medicine, University of North Texas Health Science Center, TX 2 Department of Physiology and Anatomy, University of North Texas Health Science Center, TX 3 Department of Anatomy and Cell Biology, University of Iowa, IA Osteogenesis imperfecta (OI), also known as brittle bone disease, is a genetic bone disorder caused by mutations in the genes COL1A1 and COL1A2, which are responsible for encoding type I collagen. Much is known regarding the effects of the disease on cranial and postcranial elements. However, little is known regarding the pathogenesis and physical manifestations of OI in the ear despite the high rates of hearing loss in patients with OI (~60% of the population is affected). Because ossification or demineralization of structures in the ear may affect the efficacy of certain treatments like cochlear implants, this information deficit limits the treatment options available for OI patients. Thus, the purpose of our research is to visualize and document anatomic variation in the ears of mice bred to have the Type III OI genetic variant in order to better understand the cause of OI-related hearing loss. 3D models of the middle and inner ears were created from micro-CT scans that also employed two new contrast-enhanced methods to visualize the cochlea and middle ear (malleus, incus, and stapes). All CT scanning were done on the UNTHSC campus using the new Small Animal Imaging Facility (SAIF) as part of a previous study. The scan resolution was approximately 20μm. The studied WT and OIM mouse samples include three time points intended to capture a developmental sequence: 0-day-old (WT=20, OIM=29), 7-day-old (WT=23, OIM=23), and 14-day-old mice (WT=22, OIM=18). The visualization software Avizo was then used to digitally segment the bone of the inner ear and middle ear. Gross anatomic differences are currently being documented for each region. Previous work has shown higher levels of ossification and marked bony encroachment of the otic capsule onto the cochlea in the adult OIM mouse model, potentially damaging the soft tissue of the membranous labyrinth. This research uses micro-CT imaging designed to capture a developmental sequence, giving us the potential to elucidate how and when the bony intrusions are impacting surrounding structures. Insight into this anatomical damage may help further clarify OI-related pathology, including the distinction between hearing loss associated with the middle ear (conductive hearing loss) vs. hearing loss associated with the inner ear (sensorineural hearing loss). Furthermore, a preliminary analysis of the developmental sequence should provide insight into when these anatomical changes are first occurring. Upon completion, this research will demonstrate the efficacy of using these new imaging approaches for studying minute structures of the ear and may markedly advance our understanding of the pathogenesis of OI-related hearing loss.Item Pre-weaning craniofacial development in mice with Osteogenesis Imperfecta(2024-03-21) Miller, Courtney; Emmanuel, Tanusha; Gonzales, Lauren; Handler, Emma; Organ, Jason; Menegaz, Rachel A.The craniofacial region plays a pivotal role in various physiological functions, including mastication, speech, and respiration. Early life behaviors have a profound role in shaping adult structure and function. In the early stages of life, all mammals undergo the transition from suckling to mastication, a period coinciding with rapid cranial biomineralization. Osteogenesis imperfecta (OI), a genetic disorder that impacts the production of type I collagen, disrupts biomineralization, leading to craniofacial growth differences affecting overall quality of life. This study investigates the preweaning craniofacial growth trajectory in mice OI (the OIM mouse) compared to unaffected wild type (WT mice). We hypothesize that mice with OI will exhibit smaller overall size and greater craniofacial variation than WT mice due to the abnormal collagen synthesis during skull development. Micro-CT based geometric morphometric analyses of the OIM mouse model (B6C3Fe a/a-Col1a2oim/J) were used to compare craniofacial size and shape differences at birth (P0; n=27 OIM / 20 WT) and postnatal days 7 (P7; n=21/21) and 14 (P14; n=16/20). The SlicerMorph package for 3D Slicer software was used to generate landmark point clouds for the cranium and mandible. Dimension ratios were calculated as width/length for the crania. Principal component analysis with Procrustes ANOVA were used to examine differences between genotypes at each time point, and a canonical variate analysis (CVA) used to identify shape features that maximize the distinction between genotypes across all time points. Results reveal the development of significant differences in both shape and size between the genotypes following birth. At birth, size and shape are similar between genotypes. However, by P7 and P14, OIM mice are significantly (p<0.05) smaller and display pronounced shape changes (p<0.001) characterized by larger neurocranium and shorter viscerocranium. Additionally, OIM mice have significant mandibular alterations by P7 (p<0.001) - shorter ramus, more posterior position of the coronoid, and shorter and wider dental arcade. All of these changes align with the suckling developmental stage, suggesting changes in the ratio of growth between the neurocranium and the viscerocranium during early life. Widening the neurocranium while shortening the viscerocranium during this critical developmental stage alters the masticatory muscle line of action, consequently, influences the health of individuals with OI. These findings underscore the suckling stage’s significance in shaping the foundational structures for later life, providing insights into OI craniofacial development, and suggest potential benefits to directing interventions toward an earlier time point for more effective treatment of OI.